Variant 10-23095699-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012228.4(MSRB2):c.91G>T(p.Gly31Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000863 in 1,158,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 30)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

MSRB2
NM_012228.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Variant links:

Genes affected

MSRB2 (HGNC:17061): (methionine sulfoxide reductase B2) Predicted to enable actin binding activity; peptide-methionine (R)-S-oxide reductase activity; and zinc ion binding activity. Predicted to be involved in actin filament polymerization and protein repair. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MSRB2 links:

ENSG00000286924 (HGNC:):

ENSG00000286924 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08675316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB2	NM_012228.4 linkuse as main transcript	c.91G>T	p.Gly31Cys	missense_variant	1/5	ENST00000376510.8	NP_036360.3	Q9Y3D2
MSRB2	XM_011519426.3 linkuse as main transcript	c.91G>T	p.Gly31Cys	missense_variant	1/4		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRB2	ENST00000376510.8 linkuse as main transcript	c.91G>T	p.Gly31Cys	missense_variant	1/5	1	NM_012228.4	ENSP00000365693.3		Q9Y3D2
ENSG00000286924	ENST00000655462.1 linkuse as main transcript	n.116+37990C>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.63e-7

AC:

AN:

1158590

Hom.:

Cov.:

AF XY:

0.00000179

AC XY:

AN XY:

559662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000251

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

5.7

DANN

Benign

0.37

DEOGEN2

Benign

0.16

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.29

M_CAP

Benign

0.057

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.29

REVEL

Benign

0.13

Sift

Benign

0.072

Sift4G

Uncertain

0.048

Polyphen

0.0010

Vest4

0.19

MutPred

0.32

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.22

MPC

0.20

ClinPred

0.12

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over