10-80274973-G-A

Variant names:

• chr10-80274973-G-A
• rs55855057
• NM_000429.3:c.951+44C>T

Variant summary

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

The NM_000429.3(MAT1A):​c.951+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,544,440 control chromosomes in the GnomAD database, including 13,785 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 0.10 (1028 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12757 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.231 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.951+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.951+44C>T		intron	N/A	ENSP00000361287.3
	MAT1A	ENST00000871627.1		c.951+44C>T		intron	N/A	ENSP00000541686.1
	MAT1A	ENST00000871624.1		c.1116+44C>T		intron	N/A	ENSP00000541683.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15603 AN: 152114 Hom.: 1015 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.142 AC: 21825 AN: 153890 AF XY: 0.146

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.0135

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.128 AC: 178080 AN: 1392208 Hom.: 12757 Cov.: 30 AF XY: 0.131 AC XY: 89711 AN XY: 686924

African (AFR) AF: 0.0382 AC: 1201 AN: 31418

American (AMR) AF: 0.243 AC: 8687 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2555 AN: 25156

East Asian (EAS) AF: 0.0209 AC: 747 AN: 35718

South Asian (SAS) AF: 0.235 AC: 18609 AN: 79042

European-Finnish (FIN) AF: 0.0816 AC: 3965 AN: 48590

Middle Eastern (MID) AF: 0.131 AC: 533 AN: 4078

European-Non Finnish (NFE) AF: 0.125 AC: 134613 AN: 1074840

Other (OTH) AF: 0.124 AC: 7170 AN: 57672

GnomAD4 genome AF: 0.103 AC: 15642 AN: 152232 Hom.: 1028 Cov.: 33 AF XY: 0.104 AC XY: 7736 AN XY: 74428

African (AFR) AF: 0.0429 AC: 1784 AN: 41552

American (AMR) AF: 0.192 AC: 2929 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3468

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5182

South Asian (SAS) AF: 0.243 AC: 1170 AN: 4822

European-Finnish (FIN) AF: 0.0727 AC: 771 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8238 AN: 67992

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.115 Hom.: 199

Bravo AF: 0.106

Asia WGS AF: 0.149 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.81
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs55855057; hg19: chr10-82034729; COSMIC: COSV64745396; COSMIC: COSV64745396;