NM_013283.5:c.586G>A

Variant names:

• chr5-163516577-G-A
• rs201528924
• NM_013283.5:c.586G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013283.5(MAT2B):​c.586G>A​(p.Ala196Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5	c.586G>A	p.Ala196Thr	missense_variant	Exon 5 of 7	ENST00000321757.11	NP_037415.1
MAT2B	NM_182796.2	c.553G>A	p.Ala185Thr	missense_variant	Exon 5 of 7		NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11	c.586G>A	p.Ala196Thr	missense_variant	Exon 5 of 7	1	NM_013283.5	ENSP00000325425.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	.;T;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;D;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	.;L;.;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.52
MutPred		0.55		.;Gain of ubiquitination at K191 (P = 0.0645);.;Gain of ubiquitination at K191 (P = 0.0645);
MVP		0.56
MPC		1.1
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.93
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs201528924; hg19: chr5-162943583;