5-163517635-T-G

Variant summary

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

The NM_013283.5(MAT2B):c.795T>G(p.Ile265Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.168

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=0.20273045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2B	NM_013283.5	c.795T>G	p.Ile265Met	missense_variant	6/7	ENST00000321757.11
MAT2B	NM_182796.2	c.762T>G	p.Ile254Met	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2B	ENST00000321757.11	c.795T>G	p.Ile265Met	missense_variant	6/7	1	NM_013283.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.795T>G (p.I265M) alteration is located in exon 6 (coding exon 6) of the MAT2B gene. This alteration results from a T to G substitution at nucleotide position 795, causing the isoleucine (I) at amino acid position 265 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	9.7
Dann	Benign	0.89
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.45	N;N
REVEL	Benign	0.11
Sift	Benign	0.64	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.021	B;B
Vest4		0.51
MutPred		0.72		.;Gain of disorder (P = 0.1224);
MVP		0.54
MPC		0.42
ClinPred		0.17	T
GERP RS		4.6
Varity_R		0.20
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-162944641;