rs61734474

Variant names:

• chr10-80274600-G-A
• rs61734474
• NM_000429.3:c.1005C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80274600-G-A
• chr10-80274600-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000429.3(MAT1A):​c.1005C>T​(p.Tyr335Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,614,182 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (5 hom.)
• Consequence: MAT1A NM_000429.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.17

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-80274600-G-A is Benign according to our data. Variant chr10-80274600-G-A is described in ClinVar as [Benign]. Clinvar id is 256102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (713/152302) while in subpopulation AFR AF= 0.0164 (682/41564). AF 95% confidence interval is 0.0154. There are 5 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.1005C>T	p.Tyr335Tyr	synonymous_variant	Exon 8 of 9	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.1005C>T	p.Tyr335Tyr	synonymous_variant	Exon 8 of 9	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000480845.1	n.237C>T		non_coding_transcript_exon_variant	Exon 2 of 5	3
MAT1A	ENST00000485270.5	n.517C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 711 AN: 152184 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00111 AC: 280 AN: 251476 Hom.: 4 AF XY: 0.000743 AC XY: 101 AN XY: 135914

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000505 AC: 738 AN: 1461880 Hom.: 5 Cov.: 34 AF XY: 0.000425 AC XY: 309 AN XY: 727240

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.000693

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00468 AC: 713 AN: 152302 Hom.: 5 Cov.: 33 AF XY: 0.00461 AC XY: 343 AN XY: 74482

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00527

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

Jan 22, 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	-0.61
CADD	Benign	0.49
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs61734474; hg19: chr10-82034356; COSMIC: COSV64747375; COSMIC: COSV64747375;