NM_013283.5:c.971T>A

Variant names:

• chr5-163518329-T-A
• rs192771488
• NM_013283.5:c.971T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013283.5(MAT2B):​c.971T>A​(p.Ile324Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21903339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5	c.971T>A	p.Ile324Asn	missense_variant	Exon 7 of 7	ENST00000321757.11	NP_037415.1
MAT2B	NM_182796.2	c.938T>A	p.Ile313Asn	missense_variant	Exon 7 of 7		NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11	c.971T>A	p.Ile324Asn	missense_variant	Exon 7 of 7	1	NM_013283.5	ENSP00000325425.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250214 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135284

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461120 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726858

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	.;T
Eigen	Benign	0.021
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.57	N;N
REVEL	Benign	0.095
Sift	Benign	0.041	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.42	B;P
Vest4		0.42
MutPred		0.46		.;Loss of stability (P = 0.0409);
MVP		0.49
MPC		0.86
ClinPred		0.31	T
GERP RS		5.9
Varity_R		0.39
gMVP		0.40

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: rs192771488; hg19: chr5-162945335;