rs7087728

Variant names:

• chr10-80273714-G-A
• rs7087728
• NM_000429.3:c.*67C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80273714-G-A
• chr10-80273714-G-C
• chr10-80273714-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.*67C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,141,262 control chromosomes in the GnomAD database, including 22,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3780 hom., cov: 32)
  • Exomes 𝑓: 0.19 (18839 hom.)
• Consequence: MAT1A NM_000429.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.70
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-80273714-G-A is Benign according to our data. Variant chr10-80273714-G-A is described in ClinVar as [Benign]. Clinvar id is 301184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.*67C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.*67C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000480845.1	n.487C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3
MAT1A	ENST00000485270.5	n.767C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32253 AN: 151942 Hom.: 3763 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0182

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.185 AC: 183491 AN: 989202 Hom.: 18839 Cov.: 13 AF XY: 0.188 AC XY: 96636 AN XY: 512968

African (AFR) AF: 0.287 AC: 6773 AN: 23630

American (AMR) AF: 0.298 AC: 13113 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 5462 AN: 23230

East Asian (EAS) AF: 0.0209 AC: 785 AN: 37496

South Asian (SAS) AF: 0.279 AC: 21338 AN: 76488

European-Finnish (FIN) AF: 0.144 AC: 7615 AN: 52944

Middle Eastern (MID) AF: 0.243 AC: 812 AN: 3336

European-Non Finnish (NFE) AF: 0.174 AC: 118723 AN: 683394

Other (OTH) AF: 0.199 AC: 8870 AN: 44630

GnomAD4 genome AF: 0.212 AC: 32306 AN: 152060 Hom.: 3780 Cov.: 32 AF XY: 0.211 AC XY: 15689 AN XY: 74318

African (AFR) AF: 0.283 AC: 11710 AN: 41436

American (AMR) AF: 0.272 AC: 4152 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3472

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5164

South Asian (SAS) AF: 0.288 AC: 1390 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1414 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12103 AN: 67974

Other (OTH) AF: 0.224 AC: 471 AN: 2106

Alfa AF: 0.187 Hom.: 4654

Bravo AF: 0.222

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hepatic methionine adenosyltransferase deficiency Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7087728; hg19: chr10-82033470; COSMIC: COSV64745030; COSMIC: COSV64745030;