rs17677908

Variant names:

• chr10-80289847-A-G
• rs17677908
• ENST00000871619.1:c.-255-169T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-80289847-A-G
• chr10-80289847-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000871619.1(MAT1A):​c.-255-169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,238 control chromosomes in the GnomAD database, including 1,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1025 hom., cov: 32)
• Consequence: MAT1A ENST00000871619.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109
• Publications: 2 publications found

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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-80289847-A-G is Benign according to our data. Variant chr10-80289847-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000871619.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.-424T>C		upstream_gene	N/A	NP_000420.1	Q00266

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000871619.1		c.-255-169T>C		intron	N/A	ENSP00000541678.1
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.-424T>C		upstream_gene	N/A	ENSP00000361287.3	Q00266
	MAT1A	ENST00000871627.1		c.-424T>C		upstream_gene	N/A	ENSP00000541686.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15475 AN: 152120 Hom.: 1012 Cov.: 32

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15512 AN: 152238 Hom.: 1025 Cov.: 32 AF XY: 0.103 AC XY: 7703 AN XY: 74448

African (AFR) AF: 0.0427 AC: 1776 AN: 41546

American (AMR) AF: 0.182 AC: 2776 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3468

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5190

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4818

European-Finnish (FIN) AF: 0.0719 AC: 763 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8152 AN: 67998

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.0974 Hom.: 552

Bravo AF: 0.105

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		0.11
PromoterAI		0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17677908; hg19: chr10-82049603;