chr10-80273838-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000429.3(MAT1A):​c.1131C>T​(p.Tyr377Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,610,836 control chromosomes in the GnomAD database, including 187,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23794 hom., cov: 32)
Exomes 𝑓: 0.47 ( 163800 hom. )

Consequence

MAT1A
NM_000429.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.471

Publications

34 publications found
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]
MAT1A Gene-Disease associations (from GenCC):
  • methionine adenosyltransferase deficiency
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 10-80273838-G-A is Benign according to our data. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80273838-G-A is described in CliVar as Benign. Clinvar id is 256104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.471 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAT1ANM_000429.3 linkc.1131C>T p.Tyr377Tyr synonymous_variant Exon 9 of 9 ENST00000372213.8 NP_000420.1 Q00266

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAT1AENST00000372213.8 linkc.1131C>T p.Tyr377Tyr synonymous_variant Exon 9 of 9 1 NM_000429.3 ENSP00000361287.3 Q00266
MAT1AENST00000480845.1 linkn.363C>T non_coding_transcript_exon_variant Exon 3 of 5 3
MAT1AENST00000485270.5 linkn.643C>T non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.543
AC:
82513
AN:
151940
Hom.:
23755
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.747
Gnomad AMI
AF:
0.347
Gnomad AMR
AF:
0.543
Gnomad ASJ
AF:
0.470
Gnomad EAS
AF:
0.453
Gnomad SAS
AF:
0.645
Gnomad FIN
AF:
0.424
Gnomad MID
AF:
0.481
Gnomad NFE
AF:
0.444
Gnomad OTH
AF:
0.517
GnomAD2 exomes
AF:
0.506
AC:
126549
AN:
250074
AF XY:
0.505
show subpopulations
Gnomad AFR exome
AF:
0.752
Gnomad AMR exome
AF:
0.544
Gnomad ASJ exome
AF:
0.479
Gnomad EAS exome
AF:
0.455
Gnomad FIN exome
AF:
0.429
Gnomad NFE exome
AF:
0.453
Gnomad OTH exome
AF:
0.496
GnomAD4 exome
AF:
0.468
AC:
682324
AN:
1458778
Hom.:
163800
Cov.:
38
AF XY:
0.471
AC XY:
341894
AN XY:
725856
show subpopulations
African (AFR)
AF:
0.759
AC:
25345
AN:
33414
American (AMR)
AF:
0.548
AC:
24501
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.476
AC:
12435
AN:
26112
East Asian (EAS)
AF:
0.408
AC:
16177
AN:
39682
South Asian (SAS)
AF:
0.626
AC:
53922
AN:
86198
European-Finnish (FIN)
AF:
0.429
AC:
22913
AN:
53416
Middle Eastern (MID)
AF:
0.554
AC:
3184
AN:
5744
European-Non Finnish (NFE)
AF:
0.446
AC:
494377
AN:
1109250
Other (OTH)
AF:
0.489
AC:
29470
AN:
60250
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
18692
37384
56076
74768
93460
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15176
30352
45528
60704
75880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.543
AC:
82615
AN:
152058
Hom.:
23794
Cov.:
32
AF XY:
0.545
AC XY:
40539
AN XY:
74332
show subpopulations
African (AFR)
AF:
0.747
AC:
30995
AN:
41510
American (AMR)
AF:
0.543
AC:
8301
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.470
AC:
1632
AN:
3472
East Asian (EAS)
AF:
0.454
AC:
2335
AN:
5146
South Asian (SAS)
AF:
0.646
AC:
3113
AN:
4816
European-Finnish (FIN)
AF:
0.424
AC:
4486
AN:
10570
Middle Eastern (MID)
AF:
0.493
AC:
145
AN:
294
European-Non Finnish (NFE)
AF:
0.444
AC:
30195
AN:
67940
Other (OTH)
AF:
0.519
AC:
1098
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1819
3638
5458
7277
9096
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
706
1412
2118
2824
3530
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.481
Hom.:
63527
Bravo
AF:
0.556
Asia WGS
AF:
0.573
AC:
1995
AN:
3478
EpiCase
AF:
0.455
EpiControl
AF:
0.447

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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

- -

Hepatic methionine adenosyltransferase deficiency Benign:2
Jan 13, 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

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
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
-0.73
CADD
Benign
0.26
DANN
Benign
0.33
PhyloP100
-0.47
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2993763; hg19: chr10-82033594; COSMIC: COSV64745496; COSMIC: COSV64745496; API