Genetic Variant NM_012331.5:c.203C>T (chr8-10207893-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012331.5(MSRA):c.203C>T(p.Ala68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,932 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A68D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5 link	c.203C>T	p.Ala68Val	missense_variant	Exon 2 of 6	ENST00000317173.9	NP_036463.1	Q9UJ68-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9 link	c.203C>T	p.Ala68Val	missense_variant	Exon 2 of 6	1	NM_012331.5	ENSP00000313921.4		Q9UJ68-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000806

AC:

AN:

248054

AF XY:

0.00000745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458932

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.0000224

AC:

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.00

AC:

AN:

85774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110092

Other (OTH)

AF:

0.00

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;.;T;.;.;.;.

Eigen

Benign

-0.053

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.0069

MetaRNN

Uncertain

0.56

D;D;D;D;D;D;D

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;M;.;.;.;.;.

PhyloP100

2.2

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.21

T;T;T;D;D;T;T

Sift4G

Benign

0.48

T;T;T;T;T;T;T

Polyphen

0.43

B;B;.;.;.;.;B

Vest4

0.43

MutPred

0.71

Gain of catalytic residue at A68 (P = 0.0722);Gain of catalytic residue at A68 (P = 0.0722);Gain of catalytic residue at A68 (P = 0.0722);.;.;.;.;

MVP

0.061

MPC

0.0018

ClinPred

0.77

GERP RS

4.7

Varity_R

0.33

gMVP

0.47

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over