chr8-10054614-C-T

Variant summary

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

The NM_012331.5(MSRA):​c.98C>T​(p.Pro33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,425,500 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: not found (cov: 34)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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

Genome browser will be placed here

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=0.12713516).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSRANM_012331.5 linkc.98C>T p.Pro33Leu 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
MSRAENST00000317173.9 linkc.98C>T p.Pro33Leu missense_variant Exon 1 of 6 1 NM_012331.5 ENSP00000313921.4 Q9UJ68-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD2 exomes
AF:
0.0000229
AC:
5
AN:
218014
AF XY:
0.0000167
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000132
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:
0.00000491
AC:
7
AN:
1425500
Hom.:
0
Cov.:
32
AF XY:
0.00000282
AC XY:
2
AN XY:
709090
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
29968
American (AMR)
AF:
0.0000736
AC:
3
AN:
40788
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25064
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34646
South Asian (SAS)
AF:
0.0000241
AC:
2
AN:
83032
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52824
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5670
European-Non Finnish (NFE)
AF:
9.14e-7
AC:
1
AN:
1094626
Other (OTH)
AF:
0.0000170
AC:
1
AN:
58882
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.98C>T (p.P33L) alteration is located in exon 1 (coding exon 1) of the MSRA gene. This alteration results from a C to T substitution at nucleotide position 98, causing the proline (P) at amino acid position 33 to be replaced by a leucine (L). 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
-0.23
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
D;.;T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.22
N
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.0
M;M;.
PhyloP100
2.1
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.018
D;D;D
Polyphen
0.37
B;B;.
Vest4
0.29
MutPred
0.41
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP
0.16
MPC
0.0017
ClinPred
0.96
D
GERP RS
4.0
PromoterAI
0.0092
Neutral
Varity_R
0.24
gMVP
0.40
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs373144905; hg19: chr8-9912124; API