chr8-10301561-G-A

Variant summary

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

The NM_012331.5(MSRA):​c.359G>A​(p.Arg120Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,952 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 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

4
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74
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]

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=0.24835005).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSRANM_012331.5 linkuse as main transcriptc.359G>A p.Arg120Gln missense_variant 4/6 ENST00000317173.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSRAENST00000317173.9 linkuse as main transcriptc.359G>A p.Arg120Gln missense_variant 4/61 NM_012331.5 P1Q9UJ68-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251294
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000435
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461744
Hom.:
0
Cov.:
30
AF XY:
0.0000440
AC XY:
32
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000824
AC:
10

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 submitterclinical testingAmbry GeneticsApr 22, 2022The c.359G>A (p.R120Q) alteration is located in exon 4 (coding exon 4) of the MSRA gene. This alteration results from a G to A substitution at nucleotide position 359, causing the arginine (R) at amino acid position 120 to be replaced by a glutamine (Q). 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
0.21
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Pathogenic
0.16
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.37
T;.;T;.;.;.
Eigen
Uncertain
0.63
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.25
T;T;T;T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.46
N;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N
REVEL
Benign
0.24
Sift
Benign
0.24
T;T;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T;T
Polyphen
1.0
D;D;.;.;.;D
Vest4
0.88
MVP
0.16
MPC
0.0037
ClinPred
0.39
T
GERP RS
5.7
Varity_R
0.29
gMVP
0.52

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.

Other links and lift over

dbSNP: rs183626962; hg19: chr8-10159071; API