rs299299

chr5-163505816-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
MAT2B	NM_013283.5	c.63+67T>G		intron_variant		ENST00000321757.11
MAT2B	NM_182796.2	c.30+2392T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2B	ENST00000321757.11	c.63+67T>G		intron_variant		1	NM_013283.5	P1

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

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.150

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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.162

Alfa AF: 0.175 Hom.: 300

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs299299; hg19: chr5-162932822; COSMIC: COSV55202327;