5-163513564-A-G

Variant names:

• chr5-163513564-A-G
• rs1207048090
• NM_013283.5:c.268A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013283.5(MAT2B):​c.268A>G​(p.Ile90Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000831 in 1,444,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: MAT2B NM_013283.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19765115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	NM_013283.5	MANE Select	c.268A>G	p.Ile90Val	missense	Exon 3 of 7	NP_037415.1	A0A140VJP2
	MAT2B	NM_182796.2		c.235A>G	p.Ile79Val	missense	Exon 3 of 7	NP_877725.1	Q9NZL9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2B	ENST00000321757.11	TSL:1 MANE Select	c.268A>G	p.Ile90Val	missense	Exon 3 of 7	ENSP00000325425.6	Q9NZL9-1
	MAT2B	ENST00000280969.9	TSL:1	c.235A>G	p.Ile79Val	missense	Exon 3 of 7	ENSP00000280969.5	Q9NZL9-2
	MAT2B	ENST00000518095.5	TSL:1	c.268A>G	p.Ile90Val	missense	Exon 3 of 5	ENSP00000428046.1	Q9NZL9-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250768 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000831 AC: 12 AN: 1444796 Hom.: 0 Cov.: 27 AF XY: 0.00000972 AC XY: 7 AN XY: 719962

African (AFR) AF: 0.00 AC: 0 AN: 33080

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39550

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000547 AC: 6 AN: 1097108

Other (OTH) AF: 0.0000335 AC: 2 AN: 59776

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		4.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.048
Sift	Benign	0.16	T
Sift4G	Benign	0.32	T
Polyphen		0.017	B
Vest4		0.35
MutPred		0.57		Loss of catalytic residue at A94 (P = 0.1691)
MVP		0.39
MPC		0.31
ClinPred		0.31	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.56
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1207048090; hg19: chr5-162940570;