Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:

Currentness:

HNMT T105I

(HNMT Thr105Ile)

Initial reports implicated this in causing increased susceptibility to asthma, but later reports contradict this. The variant does not appear to be significantly pathogenic, despite computational and experimental evidence that the variant affects enzyme activity.

Variant evidence
Computational	1	Model by Rutherford et al. indicates the residue affects packing, which affects the active site

Functional	2	Kidney cells with this variant and transient expression of the variant in COS-1 cells had lower HNMT activity

Case/Control		If the results of Deindl et al. are combined with Yan et al’s, the association between this variant and asthma is no longer significant. See 10803682, 15693910.

Familial	-


Clinical importance
Severity	2

Treatability	3

Penetrance	-

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

other

Allele frequency

T @ chr2:138759649: 7.7% (828/10758) in EVS
T @ chr2:138476118: 9.4% (12/128) in GET-Evidence
Frequency shown in summary reports: 7.7% (828/10758)

Publications

Kidney samples with this variant had significantly lower levels of HNMT activity & thermal stability, and COS-1 cells transiently expressing a construct with this variant had significantly lower HMNT activity.

Unable to access a copy of this paper online. OMIM reports that 192 cases and 237 were studies, with 54 alleles found in cases and 38 in controls. Counting alleles, this is case+: 54, case-: 330, control+: 38, control-: 436. This is p=0.005 and an OR of 1.88.

In a study of German children, in 261 children with asthma the allele frequency of this variant was 0.13 (similar to Yan et al), while in the 515 non-asthmatic controls the allele frequency was also 0.13. This contradicts Yan et al.‘s finding and is consistent with Sasaki et al’s negative report.

Genomes

Other external references

dbSNP

rs11558538
www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

OMIM

Asthma, susceptibility to
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605238

PolyPhen-2

Score: 0.821 (possibly damaging)

Other in silico analyses

NBLOSUM100 score = 3
GET-Evidence autoscore = 2

Edit history

Nov 29 2012 Genome Importing Robot added CGI sample GS01669-DNA_C07 from PGP sample 74521372 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_F06 from PGP sample 64191565 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_F02 from PGP sample 70008981 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_A07 from PGP sample 96240009 view
Mar 5 2012 Genome Importing Robot added hu232307 build 36 substitution variants view
Jun 23 2011 Genome Importing Robot removed [NA12156] view
Jun 23 2011 Genome Importing Robot removed [NA07022] view
Mar 29 2011 Genome Importing Robot added var-GS19704-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS19649-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS18537-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS06994-1100-36-ASM view
Mar 29 2011 Genome Importing Robot added var-GS12004-1100-36-ASM view
May 11 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited article 9547362 summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited article 15693910 summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball added article 15693910 view
May 10 2010 Madeleine Ball edited article 10803682 summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited variant summary view
May 10 2010 Madeleine Ball edited article 10803682 summary view
May 10 2010 Madeleine Ball added article 16205835 view
May 10 2010 Madeleine Ball added article 10752634 view
May 10 2010 Madeleine Ball added article 18154359 view
May 10 2010 Madeleine Ball added article 10803682 view
May 10 2010 Madeleine Ball added article 9547362 view
May 8 2010 Genome Importing Robot added CGI sample GS00253-DNA_A02_200_37 view
Feb 26 2010 Genome Importing Robot added [NA12156] view
Jan 12 2010 Abraham Rosenbaum edited variant summary view
Jan 5 2010 OMIM Importing Robot edited variant summary view
Dec 27 2009 Genome Importing Robot added [NA07022] view
Dec 27 2009 Genome Importing Robot added [NA12878] view
Dec 27 2009 Genome Importing Robot added variant view

HNMT T105I - GET-Evidence

HNMT T105I

Allele frequency

Publications

Genomes

Other external references

Other in silico analyses

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HNMT T105I - GET-Evidence

HNMT T105I

Allele frequency

Publications

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Genomes

Other external references

Other in silico analyses

Edit history

Gene search

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