Variant 12-65278795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000355192.8(MSRB3):c.27C>T(p.Arg9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,571,350 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

MSRB3
ENST00000355192.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.30

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-65278795-C-T is Benign according to our data. Variant chr12-65278795-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65278795-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000151 (23/152034) while in subpopulation SAS AF= 0.00104 (5/4824). AF 95% confidence interval is 0.000408. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MSRB3	NM_001031679.3 linkuse as main transcript	c.-122C>T		5_prime_UTR_variant	1/7	ENST00000308259.10
MSRB3	NM_198080.4 linkuse as main transcript	c.27C>T	p.Arg9=	synonymous_variant	1/6
MSRB3	NM_001193460.2 linkuse as main transcript	c.-286C>T		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRB3	ENST00000308259.10 linkuse as main transcript	c.-122C>T		5_prime_UTR_variant	1/7	1	NM_001031679.3	P1	Q8IXL7-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000455

AC:

AN:

180080

Hom.:

AF XY:

0.000571

AC XY:

AN XY:

96402

show subpopulations

Gnomad AFR exome

AF:

0.0000998

Gnomad AMR exome

AF:

0.000655

Gnomad ASJ exome

AF:

0.000114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00177

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.000236

AC:

335

AN:

1419316

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

196

AN XY:

702042

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.000854

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000907

Gnomad4 OTH exome

AF:

0.000323

GnomAD4 genome

AF:

0.000151

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000308

Hom.:

Bravo

AF:

0.000215

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	MSRB3: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over