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 VariationId 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.

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.*67C>T		3_prime_UTR	Exon 9 of 9	NP_000420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT1A	ENST00000372213.8	TSL:1 MANE Select	c.*67C>T		3_prime_UTR	Exon 9 of 9	ENSP00000361287.3
	MAT1A	ENST00000480845.1	TSL:3	n.487C>T		non_coding_transcript_exon	Exon 3 of 5
	MAT1A	ENST00000485270.5	TSL:2	n.767C>T		non_coding_transcript_exon	Exon 3 of 3

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hepatic methionine adenosyltransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

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;