chr8-10054643-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012331.5(MSRA):ā€‹c.127C>Gā€‹(p.Gln43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,571,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 34)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.71
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039508075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSRANM_012331.5 linkuse as main transcriptc.127C>G p.Gln43Glu missense_variant 1/6 ENST00000317173.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSRAENST00000317173.9 linkuse as main transcriptc.127C>G p.Gln43Glu missense_variant 1/61 NM_012331.5 P1Q9UJ68-1
ENST00000659604.1 linkuse as main transcriptn.116+283G>C intron_variant, non_coding_transcript_variant
MSRAENST00000518255.5 linkuse as main transcriptc.127C>G p.Gln43Glu missense_variant 1/65
MSRAENST00000441698.6 linkuse as main transcriptc.127C>G p.Gln43Glu missense_variant 1/52 Q9UJ68-4

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152014
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000237
AC:
5
AN:
211224
Hom.:
0
AF XY:
0.00000861
AC XY:
1
AN XY:
116136
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000683
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000311
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000176
AC:
25
AN:
1419166
Hom.:
0
Cov.:
32
AF XY:
0.0000184
AC XY:
13
AN XY:
705932
show subpopulations
Gnomad4 AFR exome
AF:
0.0000337
Gnomad4 AMR exome
AF:
0.0000502
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000202
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152014
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2023The c.127C>G (p.Q43E) alteration is located in exon 1 (coding exon 1) of the MSRA gene. This alteration results from a C to G substitution at nucleotide position 127, causing the glutamine (Q) at amino acid position 43 to be replaced by a glutamic acid (E). 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
0.077
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
1.1
DANN
Benign
0.83
DEOGEN2
Benign
0.14
T;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.027
N
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.040
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.86
N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.080
N;N;N
REVEL
Benign
0.0020
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.27
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.078
MutPred
0.23
Loss of methylation at K41 (P = 0.0778);Loss of methylation at K41 (P = 0.0778);Loss of methylation at K41 (P = 0.0778);
MVP
0.16
MPC
0.0016
ClinPred
0.027
T
GERP RS
-3.8
Varity_R
0.068
gMVP
0.18

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: rs778639208; hg19: chr8-9912153; API