rs2994388

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000429.3(MAT1A):​c.1085+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,602 control chromosomes in the GnomAD database, including 187,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23804 hom., cov: 32)
Exomes 𝑓: 0.47 ( 163917 hom. )

Consequence

MAT1A
NM_000429.3 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.117
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 10-80274506-G-A is Benign according to our data. Variant chr10-80274506-G-A is described in ClinVar as [Benign]. Clinvar id is 256103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-80274506-G-A is described in Lovd as [Benign].
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/exons MANE UniProt
MAT1ANM_000429.3 linkuse as main transcriptc.1085+14C>T intron_variant ENST00000372213.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAT1AENST00000372213.8 linkuse as main transcriptc.1085+14C>T intron_variant 1 NM_000429.3 P1
MAT1AENST00000480845.1 linkuse as main transcriptn.317+14C>T intron_variant, non_coding_transcript_variant 3
MAT1AENST00000485270.5 linkuse as main transcriptn.597+14C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.543
AC:
82509
AN:
151952
Hom.:
23765
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.747
Gnomad AMI
AF:
0.345
Gnomad AMR
AF:
0.542
Gnomad ASJ
AF:
0.470
Gnomad EAS
AF:
0.452
Gnomad SAS
AF:
0.645
Gnomad FIN
AF:
0.424
Gnomad MID
AF:
0.484
Gnomad NFE
AF:
0.444
Gnomad OTH
AF:
0.516
GnomAD3 exomes
AF:
0.506
AC:
127090
AN:
251288
Hom.:
33272
AF XY:
0.505
AC XY:
68547
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.753
Gnomad AMR exome
AF:
0.544
Gnomad ASJ exome
AF:
0.479
Gnomad EAS exome
AF:
0.455
Gnomad SAS exome
AF:
0.624
Gnomad FIN exome
AF:
0.430
Gnomad NFE exome
AF:
0.453
Gnomad OTH exome
AF:
0.496
GnomAD4 exome
AF:
0.468
AC:
683826
AN:
1461532
Hom.:
163917
Cov.:
49
AF XY:
0.471
AC XY:
342566
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.759
Gnomad4 AMR exome
AF:
0.548
Gnomad4 ASJ exome
AF:
0.476
Gnomad4 EAS exome
AF:
0.408
Gnomad4 SAS exome
AF:
0.625
Gnomad4 FIN exome
AF:
0.429
Gnomad4 NFE exome
AF:
0.446
Gnomad4 OTH exome
AF:
0.489
GnomAD4 genome
AF:
0.543
AC:
82611
AN:
152070
Hom.:
23804
Cov.:
32
AF XY:
0.546
AC XY:
40551
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.747
Gnomad4 AMR
AF:
0.543
Gnomad4 ASJ
AF:
0.470
Gnomad4 EAS
AF:
0.453
Gnomad4 SAS
AF:
0.646
Gnomad4 FIN
AF:
0.424
Gnomad4 NFE
AF:
0.444
Gnomad4 OTH
AF:
0.519
Alfa
AF:
0.465
Hom.:
29888
Bravo
AF:
0.556
Asia WGS
AF:
0.573
AC:
1995
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Hepatic methionine adenosyltransferase deficiency Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.13
DANN
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs2994388; hg19: chr10-82034262; COSMIC: COSV64745501; COSMIC: COSV64745501; API