Genetic Variant MSRA:p.Ser32Gly (chr8-10054610-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012331.5(MSRA):c.94A>G(p.Ser32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0640

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:

MSRA-DT (HGNC:55400): (MSRA divergent transcript)

MSRA-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09184548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSRA	NM_012331.5 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 1 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.94A>G	p.Ser32Gly	missense_variant	Exon 1 of 6	1	NM_012331.5	ENSP00000313921.4		Q9UJ68-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

218696

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709560

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30052

American (AMR)

AF:

0.00

AC:

AN:

40920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

34816

South Asian (SAS)

AF:

0.00

AC:

AN:

83166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095054

Other (OTH)

AF:

0.00

AC:

AN:

58904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.94A>G (p.S32G) alteration is located in exon 1 (coding exon 1) of the MSRA gene. This alteration results from a A to G substitution at nucleotide position 94, causing the serine (S) at amino acid position 32 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.40

T;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.077

M_CAP

Benign

0.0066

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;.

PhyloP100

-0.064

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.076

Sift

Uncertain

0.028

D;D;D

Sift4G

Benign

0.069

T;T;D

Polyphen

0.44

B;P;.

Vest4

0.14

MutPred

0.24

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.055

MPC

0.0017

ClinPred

0.47

GERP RS

-0.53

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.095

gMVP

0.38

Mutation Taster

=95/5

polymorphism

(source)

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

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8-10054610-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over