12-65281848-T-C

Position:

• chr12-65281848-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031679.3(MSRB3):​c.-52+2983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,074 control chromosomes in the GnomAD database, including 6,559 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 0.29 (6559 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

Genes affected

MSRB3 (HGNC:27375): (methionine sulfoxide reductase B3) The protein encoded by this gene catalyzes the reduction of methionine sulfoxide to methionine. This enzyme acts as a monomer and requires zinc as a cofactor. Several transcript variants encoding two different isoforms have been found for this gene. One of the isoforms localizes to mitochondria while the other localizes to endoplasmic reticula. [provided by RefSeq, Jul 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRB3	NM_001031679.3	c.-52+2983T>C		intron_variant		ENST00000308259.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB3	ENST00000308259.10	c.-52+2983T>C		intron_variant		1	NM_001031679.3	P1
	ENST00000545709.1	n.192T>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44376 AN: 151954 Hom.: 6544 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.292 AC: 44413 AN: 152072 Hom.: 6559 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74340

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.264

Alfa AF: 0.298 Hom.: 4056

Bravo AF: 0.295

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.77

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: rs1344945; hg19: chr12-65675628;