10-80280296-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000429.3(MAT1A):​c.426T>C​(p.Ala142Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,613,670 control chromosomes in the GnomAD database, including 409,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46318 hom., cov: 30)
Exomes 𝑓: 0.70 ( 362787 hom. )

Consequence

MAT1A
NM_000429.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.585
Variant links:
Genes affected
MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 10-80280296-A-G is Benign according to our data. Variant chr10-80280296-A-G is described in ClinVar as [Benign]. Clinvar id is 256105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80280296-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.585 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAT1ANM_000429.3 linkc.426T>C p.Ala142Ala synonymous_variant Exon 5 of 9 ENST00000372213.8 NP_000420.1 Q00266

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAT1AENST00000372213.8 linkc.426T>C p.Ala142Ala synonymous_variant Exon 5 of 9 1 NM_000429.3 ENSP00000361287.3 Q00266
MAT1AENST00000455001.1 linkc.237T>C p.Ala79Ala synonymous_variant Exon 4 of 5 5 ENSP00000414961.1 B1ANE6

Frequencies

GnomAD3 genomes
AF:
0.770
AC:
116921
AN:
151772
Hom.:
46259
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.936
Gnomad AMI
AF:
0.609
Gnomad AMR
AF:
0.782
Gnomad ASJ
AF:
0.748
Gnomad EAS
AF:
0.968
Gnomad SAS
AF:
0.853
Gnomad FIN
AF:
0.697
Gnomad MID
AF:
0.782
Gnomad NFE
AF:
0.661
Gnomad OTH
AF:
0.764
GnomAD3 exomes
AF:
0.756
AC:
190035
AN:
251342
Hom.:
73325
AF XY:
0.751
AC XY:
102030
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.936
Gnomad AMR exome
AF:
0.816
Gnomad ASJ exome
AF:
0.756
Gnomad EAS exome
AF:
0.975
Gnomad SAS exome
AF:
0.836
Gnomad FIN exome
AF:
0.699
Gnomad NFE exome
AF:
0.667
Gnomad OTH exome
AF:
0.734
GnomAD4 exome
AF:
0.700
AC:
1022897
AN:
1461780
Hom.:
362787
Cov.:
63
AF XY:
0.702
AC XY:
510239
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.944
Gnomad4 AMR exome
AF:
0.814
Gnomad4 ASJ exome
AF:
0.755
Gnomad4 EAS exome
AF:
0.948
Gnomad4 SAS exome
AF:
0.835
Gnomad4 FIN exome
AF:
0.697
Gnomad4 NFE exome
AF:
0.665
Gnomad4 OTH exome
AF:
0.734
GnomAD4 genome
AF:
0.771
AC:
117040
AN:
151890
Hom.:
46318
Cov.:
30
AF XY:
0.775
AC XY:
57513
AN XY:
74196
show subpopulations
Gnomad4 AFR
AF:
0.936
Gnomad4 AMR
AF:
0.782
Gnomad4 ASJ
AF:
0.748
Gnomad4 EAS
AF:
0.967
Gnomad4 SAS
AF:
0.852
Gnomad4 FIN
AF:
0.697
Gnomad4 NFE
AF:
0.661
Gnomad4 OTH
AF:
0.766
Alfa
AF:
0.700
Hom.:
54605
Bravo
AF:
0.784
Asia WGS
AF:
0.891
AC:
3096
AN:
3478
EpiCase
AF:
0.673
EpiControl
AF:
0.670

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hepatic methionine adenosyltransferase deficiency Benign:2
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
5.5
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1143694; hg19: chr10-82040052; COSMIC: COSV64746096; COSMIC: COSV64746096; API