Variant 8-10319888-C-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_012331.5(MSRA):c.442C>T(p.Arg148Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,541,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

MSRA 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=0.24974006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSRA	NM_012331.5 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	5/6	ENST00000317173.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSRA	ENST00000317173.9 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	5/6	1	NM_012331.5	P1	Q9UJ68-1

Frequencies

GnomAD3 genomes

AF:

0.000757

AC:

115

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000210

AC:

AN:

214546

Hom.:

AF XY:

0.000198

AC XY:

AN XY:

115920

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.0000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000986

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.000137

AC:

191

AN:

1389588

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

685740

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.0000821

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000848

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152132

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.000861

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

AC:

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

Oct 03, 2022

The c.442C>T (p.R148C) alteration is located in exon 5 (coding exon 5) of the MSRA gene. This alteration results from a C to T substitution at nucleotide position 442, causing the arginine (R) at amino acid position 148 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Pathogenic

0.34

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Pathogenic

0.91

D;.;T;.;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.068

MetaRNN

Benign

0.23

T;T;T;T;T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

4.1

H;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.6

D;D;D;D;D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;D

Vest4

0.89

MVP

0.26

MPC

0.0032

ClinPred

0.90

GERP RS

5.6

Varity_R

0.86

gMVP

0.62

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