chr12-65282462-T-C

Variant names:

• chr12-65282462-T-C
• rs7132313
• NM_001031679.3:c.-52+3597T>C

Variant summary

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

The NM_001031679.3(MSRB3):​c.-52+3597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,178 control chromosomes in the GnomAD database, including 1,935 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 0.097 (1935 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 0 publications found

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]

MSRB3 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 74

  Inheritance: AR, Unknown Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000250280 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRB3	NM_001031679.3	c.-52+3597T>C		intron_variant	Intron 1 of 6	ENST00000308259.10	NP_001026849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRB3	ENST00000308259.10	c.-52+3597T>C		intron_variant	Intron 1 of 6	1	NM_001031679.3	ENSP00000312274.6

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14730 AN: 152060 Hom.: 1927 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.00688

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0971 AC: 14771 AN: 152178 Hom.: 1935 Cov.: 32 AF XY: 0.0954 AC XY: 7101 AN XY: 74444

African (AFR) AF: 0.294 AC: 12200 AN: 41478

American (AMR) AF: 0.0394 AC: 602 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.0650 AC: 336 AN: 5168

South Asian (SAS) AF: 0.0881 AC: 425 AN: 4824

European-Finnish (FIN) AF: 0.00688 AC: 73 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 905 AN: 68010

Other (OTH) AF: 0.0724 AC: 153 AN: 2112

Alfa AF: 0.0546 Hom.: 241

Bravo AF: 0.107

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.24
PhyloP100		-0.47
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: rs7132313; hg19: chr12-65676242;