10-80273927-G-A

Variant names:

• chr10-80273927-G-A
• rs4933327
• NM_000429.3:c.1086-44C>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.1086-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,348,844 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3277 hom., cov: 33)
  • Exomes 𝑓: 0.22 (29763 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.141
• Publications: 10 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=-0.82).
• BP6: Variant 10-80273927-G-A is Benign according to our data. Variant chr10-80273927-G-A is described in ClinVar as Benign. ClinVar VariationId is 1223539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 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.1086-44C>T		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.1086-44C>T		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000480845.1	TSL:3	n.318-44C>T		intron	N/A
	MAT1A	ENST00000485270.5	TSL:2	n.598-44C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29798 AN: 152106 Hom.: 3268 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.200

GnomAD2 exomes AF: 0.234 AC: 58107 AN: 248682 AF XY: 0.238

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.440

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.215 AC: 257632 AN: 1196620 Hom.: 29763 Cov.: 17 AF XY: 0.218 AC XY: 132649 AN XY: 608782

African (AFR) AF: 0.113 AC: 3080 AN: 27256

American (AMR) AF: 0.212 AC: 9394 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3437 AN: 24454

East Asian (EAS) AF: 0.383 AC: 14722 AN: 38432

South Asian (SAS) AF: 0.296 AC: 23823 AN: 80370

European-Finnish (FIN) AF: 0.226 AC: 12015 AN: 53234

Middle Eastern (MID) AF: 0.237 AC: 1222 AN: 5158

European-Non Finnish (NFE) AF: 0.205 AC: 178937 AN: 872066

Other (OTH) AF: 0.214 AC: 11002 AN: 51308

GnomAD4 genome AF: 0.196 AC: 29823 AN: 152224 Hom.: 3277 Cov.: 33 AF XY: 0.201 AC XY: 14973 AN XY: 74408

African (AFR) AF: 0.121 AC: 5035 AN: 41546

American (AMR) AF: 0.205 AC: 3141 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2243 AN: 5166

South Asian (SAS) AF: 0.319 AC: 1537 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2429 AN: 10590

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14283 AN: 68012

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.204 Hom.: 4484

Bravo AF: 0.191

Asia WGS AF: 0.356 AC: 1235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.44
DANN	Benign	0.76
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs4933327; hg19: chr10-82033683; COSMIC: COSV64745789; COSMIC: COSV64745789;