rs4934028

Variant names:

• chr10-80279023-G-A
• rs4934028
• NM_000429.3:c.549+1150C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80279023-G-A
• chr10-80279023-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000429.3(MAT1A):​c.549+1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,058 control chromosomes in the GnomAD database, including 21,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21028 hom., cov: 33)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 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.549+1150C>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.549+1150C>T		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000455001.1	TSL:5	c.360+1150C>T		intron	N/A	ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77742 AN: 151940 Hom.: 20989 Cov.: 33

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.512 AC: 77849 AN: 152058 Hom.: 21028 Cov.: 33 AF XY: 0.513 AC XY: 38130 AN XY: 74318

African (AFR) AF: 0.692 AC: 28698 AN: 41466

American (AMR) AF: 0.527 AC: 8052 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2342 AN: 5176

South Asian (SAS) AF: 0.613 AC: 2958 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4072 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28670 AN: 67978

Other (OTH) AF: 0.509 AC: 1076 AN: 2116

Alfa AF: 0.452 Hom.: 26942

Bravo AF: 0.528

Asia WGS AF: 0.556 AC: 1936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.77
PhyloP100		0.20
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: rs4934028; hg19: chr10-82038779;