Genetic Variant MSRB3:c.-110C>G (chr12-65278807-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031679.3(MSRB3):c.-110C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MSRB3
NM_001031679.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.655

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 Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MSRB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.044).

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	Effect	Exon Rank	Protein	UniProt
MSRB3	NM_001031679.3	MANE Select	c.-110C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001026849.1	Q8IXL7-2
MSRB3	NM_001031679.3	MANE Select	c.-110C>G	5_prime_UTR	Exon 1 of 7	NP_001026849.1	Q8IXL7-2
MSRB3	NM_001193460.2		c.-274C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001180389.1	Q8IXL7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSRB3	ENST00000308259.10	TSL:1 MANE Select	c.-110C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000312274.6	Q8IXL7-2
MSRB3	ENST00000535664.5	TSL:1	c.-274C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000441650.1	Q8IXL7-2
MSRB3	ENST00000355192.8	TSL:1	c.39C>G	p.Leu13Leu	synonymous	Exon 1 of 6	ENSP00000347324.3	Q8IXL7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418898

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32358

American (AMR)

AF:

0.00

AC:

AN:

38334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25340

East Asian (EAS)

AF:

0.00

AC:

AN:

37328

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090492

Other (OTH)

AF:

0.00

AC:

AN:

58852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.66

PromoterAI

-0.013

Neutral

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over