Variant 10-23104221-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000376510.8(MSRB2):c.196A>G(p.Thr66Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,613,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

MSRB2
ENST00000376510.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

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:

(HGNC:):

links:

Genome browser will be placed here

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=0.07840693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRB2	NM_012228.4 linkuse as main transcript	c.196A>G	p.Thr66Ala	missense_variant	2/5	ENST00000376510.8	NP_036360.3
MSRB2	XM_011519426.3 linkuse as main transcript	c.196A>G	p.Thr66Ala	missense_variant	2/4		XP_011517728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MSRB2	ENST00000376510.8 linkuse as main transcript	c.196A>G	p.Thr66Ala	missense_variant	2/5	1	NM_012228.4	ENSP00000365693	P1
	ENST00000655462.1 linkuse as main transcript	n.116+29468T>C		intron_variant, non_coding_transcript_variant
MSRB2	ENST00000472663.1 linkuse as main transcript	c.79A>G	p.Thr27Ala	missense_variant, NMD_transcript_variant	1/5	5		ENSP00000434990

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000984

AC:

244

AN:

247968

Hom.:

AF XY:

0.000973

AC XY:

131

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.000832

GnomAD4 exome

AF:

0.00134

AC:

1951

AN:

1461352

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

897

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.000958

AC:

146

AN:

152352

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00102

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000775

AC:

ESP6500EA

AF:

0.00181

AC:

ExAC

AF:

0.000935

AC:

113

EpiCase

AF:

0.00214

EpiControl

AF:

0.00190

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.196A>G (p.T66A) alteration is located in exon 2 (coding exon 2) of the MSRB2 gene. This alteration results from a A to G substitution at nucleotide position 196, causing the threonine (T) at amino acid position 66 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.037

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.44

Sift

Benign

0.18

Sift4G

Benign

0.19

Polyphen

0.38

Vest4

0.50

MVP

0.82

MPC

0.66

ClinPred

0.048

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.15

gMVP

0.64

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