rs10887721

Variant names:

• chr10-80285598-G-C
• rs10887721
• NM_000429.3:c.92-9C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-80285598-G-C
• chr10-80285598-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.92-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,587,578 control chromosomes in the GnomAD database, including 22,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5159 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17032 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Scores: Splicing: ADA: 0.4505
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.300
• Publications: 9 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: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-80285598-G-C is Benign according to our data. Variant chr10-80285598-G-C is described in ClinVar as Benign. ClinVar VariationId is 256108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000429.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	NM_000429.3	MANE Select	c.92-9C>G		intron	N/A	NP_000420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.92-9C>G		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000455001.1	TSL:5	c.26-9C>G		intron	N/A	ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32849 AN: 151980 Hom.: 5144 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.138 AC: 34758 AN: 251282 AF XY: 0.136

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.0758

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.142 AC: 203208 AN: 1435480 Hom.: 17032 Cov.: 27 AF XY: 0.140 AC XY: 100100 AN XY: 715876

African (AFR) AF: 0.461 AC: 15238 AN: 33038

American (AMR) AF: 0.0827 AC: 3697 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4648 AN: 25958

East Asian (EAS) AF: 0.000531 AC: 21 AN: 39574

South Asian (SAS) AF: 0.103 AC: 8850 AN: 85684

European-Finnish (FIN) AF: 0.115 AC: 6148 AN: 53410

Middle Eastern (MID) AF: 0.170 AC: 974 AN: 5716

European-Non Finnish (NFE) AF: 0.142 AC: 154902 AN: 1087960

Other (OTH) AF: 0.147 AC: 8730 AN: 59456

GnomAD4 genome AF: 0.216 AC: 32893 AN: 152098 Hom.: 5159 Cov.: 32 AF XY: 0.212 AC XY: 15745 AN XY: 74356

African (AFR) AF: 0.446 AC: 18487 AN: 41464

American (AMR) AF: 0.129 AC: 1968 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0914 AC: 440 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9632 AN: 67980

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.171 Hom.: 850

Bravo AF: 0.229

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.56
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.45
dbscSNV1_RF	Benign	0.37
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

Other links and lift over

dbSNP: rs10887721; hg19: chr10-82045354;