rs10506523

Variant names:

• chr12-65442727-C-G
• rs10506523
• NM_001031679.3:c.293-11001C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001031679.3(MSRB3):​c.293-11001C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 152,118 control chromosomes in the GnomAD database, including 156 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 0.032 (156 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 2 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 Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031679.3. 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
	MSRB3	NM_001031679.3	MANE Select	c.293-11001C>G		intron	N/A	NP_001026849.1	Q8IXL7-2
	MSRB3	NM_198080.4		c.314-11001C>G		intron	N/A	NP_932346.1	Q8IXL7-1
	MSRB3	NM_001193460.2		c.293-11001C>G		intron	N/A	NP_001180389.1	Q8IXL7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRB3	ENST00000308259.10	TSL:1 MANE Select	c.293-11001C>G		intron	N/A	ENSP00000312274.6	Q8IXL7-2
	MSRB3	ENST00000355192.8	TSL:1	c.314-11001C>G		intron	N/A	ENSP00000347324.3	Q8IXL7-1
	MSRB3	ENST00000535664.5	TSL:1	c.293-11001C>G		intron	N/A	ENSP00000441650.1	Q8IXL7-2

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4871 AN: 152000 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0291

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

GnomAD4 genome AF: 0.0322 AC: 4899 AN: 152118 Hom.: 156 Cov.: 32 AF XY: 0.0327 AC XY: 2429 AN XY: 74380

African (AFR) AF: 0.0712 AC: 2954 AN: 41502

American (AMR) AF: 0.0183 AC: 280 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.0498 AC: 258 AN: 5180

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4828

European-Finnish (FIN) AF: 0.0293 AC: 311 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 764 AN: 67944

Other (OTH) AF: 0.0354 AC: 75 AN: 2116

Alfa AF: 0.0229 Hom.: 14

Bravo AF: 0.0314

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10506523; hg19: chr12-65836507;