Genetic Variant NM_001031679.3:c.55C>G (chr12-65308634-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001031679.3(MSRB3):c.55C>G(p.Arg19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MSRB3
NM_001031679.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.05

Publications

0 publications found

Variant links:

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

MSRB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3287689).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MSRB3	NM_001031679.3	MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 7	NP_001026849.1
MSRB3	NM_001193460.2		c.55C>G	p.Arg19Gly	missense	Exon 3 of 8	NP_001180389.1
MSRB3	NM_001193461.2		c.55C>G	p.Arg19Gly	missense	Exon 2 of 7	NP_001180390.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MSRB3	ENST00000308259.10	TSL:1 MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 7	ENSP00000312274.6
MSRB3	ENST00000535664.5	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 3 of 8	ENSP00000441650.1
MSRB3	ENST00000355192.8	TSL:1	c.98-18192C>G		intron	N/A	ENSP00000347324.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111866

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

0.12

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.044

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.78

PhyloP100

3.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Benign

0.20

Sift4G

Uncertain

0.054

Polyphen

0.79

Vest4

0.78

MutPred

0.49

Gain of sheet (P = 0.0061)

MVP

0.71

ClinPred

0.38

GERP RS

5.1

Mutation Taster

=84/16

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over