8-10301626-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012331.5(MSRA):ā€‹c.424G>Cā€‹(p.Asp142His) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.000094 ( 0 hom. )

Consequence

MSRA
NM_012331.5 missense

Scores

7
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MSRANM_012331.5 linkuse as main transcriptc.424G>C p.Asp142His missense_variant 4/6 ENST00000317173.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MSRAENST00000317173.9 linkuse as main transcriptc.424G>C p.Asp142His missense_variant 4/61 NM_012331.5 P1Q9UJ68-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000147
AC:
37
AN:
251360
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000937
AC:
137
AN:
1461478
Hom.:
0
Cov.:
30
AF XY:
0.000103
AC XY:
75
AN XY:
727052
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00131
Gnomad4 SAS exome
AF:
0.000533
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000173
AC:
21
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsOct 13, 2023The c.424G>C (p.D142H) alteration is located in exon 4 (coding exon 4) of the MSRA gene. This alteration results from a G to C substitution at nucleotide position 424, causing the aspartic acid (D) at amino acid position 142 to be replaced by a histidine (H). 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
Pathogenic
0.68
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.93
D;.;T;.;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.58
D;D;D;D;D;D
MetaSVM
Uncertain
0.48
D
MutationAssessor
Pathogenic
4.5
H;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.4
D;D;D;D;D;D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0010
D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;D;.;.;.;D
Vest4
0.86
MVP
0.43
MPC
0.0036
ClinPred
0.64
D
GERP RS
5.7
Varity_R
0.74
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs371090925; hg19: chr8-10159136; API