chr12-65324519-T-G

Variant names:

• chr12-65324519-T-G
• rs17178006
• NM_001031679.3:c.77-2307T>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.77-2307T>G variant causes a intron change. The variant allele was found at a frequency of 0.0635 in 152,238 control chromosomes in the GnomAD database, including 415 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 0.064 (415 hom., cov: 32)
• Consequence: MSRB3 NM_001031679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 36 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRB3	NM_001031679.3	MANE Select	c.77-2307T>G		intron	N/A	NP_001026849.1
	MSRB3	NM_198080.4		c.98-2307T>G		intron	N/A	NP_932346.1
	MSRB3	NM_001193460.2		c.77-2307T>G		intron	N/A	NP_001180389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSRB3	ENST00000308259.10	TSL:1 MANE Select	c.77-2307T>G		intron	N/A	ENSP00000312274.6
	MSRB3	ENST00000355192.8	TSL:1	c.98-2307T>G		intron	N/A	ENSP00000347324.3
	MSRB3	ENST00000535664.5	TSL:1	c.77-2307T>G		intron	N/A	ENSP00000441650.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9676 AN: 152120 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0635 AC: 9670 AN: 152238 Hom.: 415 Cov.: 32 AF XY: 0.0594 AC XY: 4419 AN XY: 74430

African (AFR) AF: 0.0195 AC: 810 AN: 41538

American (AMR) AF: 0.0627 AC: 959 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3468

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5192

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4828

European-Finnish (FIN) AF: 0.0598 AC: 634 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6870 AN: 67998

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0818 Hom.: 1411

Bravo AF: 0.0624

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.86
PhyloP100		4.7
Mutation Taster		=98/2	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: rs17178006; hg19: chr12-65718299;