NM_013283.5:c.63+67T>G

Variant names:

• chr5-163505816-T-G
• rs299299
• NM_013283.5:c.63+67T>G

Variant summary

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

The NM_013283.5(MAT2B):​c.63+67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,208,942 control chromosomes in the GnomAD database, including 15,327 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 0.17 (2263 hom., cov: 31)
  • Exomes 𝑓: 0.16 (13064 hom.)
• Consequence: MAT2B NM_013283.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5	c.63+67T>G		intron_variant	Intron 1 of 6	ENST00000321757.11	NP_037415.1
MAT2B	NM_182796.2	c.30+2392T>G		intron_variant	Intron 1 of 6		NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11	c.63+67T>G		intron_variant	Intron 1 of 6	1	NM_013283.5	ENSP00000325425.6

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25381 AN: 151886 Hom.: 2262 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0697

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.156 AC: 164793 AN: 1056938 Hom.: 13064 AF XY: 0.156 AC XY: 78229 AN XY: 500162

African (AFR) AF: 0.193 AC: 4287 AN: 22206

American (AMR) AF: 0.123 AC: 1028 AN: 8388

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 2171 AN: 14124

East Asian (EAS) AF: 0.102 AC: 2699 AN: 26362

South Asian (SAS) AF: 0.133 AC: 2503 AN: 18806

European-Finnish (FIN) AF: 0.229 AC: 8356 AN: 36490

Middle Eastern (MID) AF: 0.204 AC: 608 AN: 2978

European-Non Finnish (NFE) AF: 0.155 AC: 136759 AN: 885072

Other (OTH) AF: 0.150 AC: 6382 AN: 42512

GnomAD4 genome AF: 0.167 AC: 25402 AN: 152004 Hom.: 2263 Cov.: 31 AF XY: 0.168 AC XY: 12496 AN XY: 74290

African (AFR) AF: 0.185 AC: 7655 AN: 41464

American (AMR) AF: 0.131 AC: 1995 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3466

East Asian (EAS) AF: 0.0701 AC: 361 AN: 5152

South Asian (SAS) AF: 0.132 AC: 637 AN: 4812

European-Finnish (FIN) AF: 0.229 AC: 2423 AN: 10570

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11167 AN: 67946

Other (OTH) AF: 0.162 AC: 341 AN: 2108

Alfa AF: 0.175 Hom.: 310

Bravo AF: 0.163

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.36
PhyloP100		-2.3
PromoterAI		-0.031	Neutral
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: rs299299; hg19: chr5-162932822; COSMIC: COSV55202327;