GeneBe

rs755928429

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP7

The NM_012331.5(MSRA):​c.118C>A​(p.Arg40Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,423,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MSRA
NM_012331.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

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 (BayesDel_noAF=-0.15).
BP7
Synonymous conserved (PhyloP=2.03 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSRANM_012331.5 linkc.118C>A p.Arg40Arg synonymous_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.118C>A p.Arg40Arg synonymous_variant Exon 1 of 6 1 NM_012331.5 ENSP00000313921.4 Q9UJ68-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1423932
Hom.:
0
Cov.:
32
AF XY:
0.00000282
AC XY:
2
AN XY:
708342
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
29902
American (AMR)
AF:
0.00
AC:
0
AN:
40588
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24996
East Asian (EAS)
AF:
0.0000290
AC:
1
AN:
34468
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82940
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52732
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5668
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1093838
Other (OTH)
AF:
0.0000170
AC:
1
AN:
58800
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.15
CADD
Benign
13
DANN
Benign
0.96
PhyloP100
2.0
PromoterAI
-0.17
Neutral

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: rs755928429; hg19: chr8-9912144; API