GeneBe

chr8-10054582-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_012331.5(MSRA):​c.66G>A​(p.Arg22Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,952 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: 7.0e-7 ( 0 hom. )

Consequence

MSRA
NM_012331.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.661

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)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP7
Synonymous conserved (PhyloP=0.661 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSRANM_012331.5 linkc.66G>A p.Arg22Arg 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.66G>A p.Arg22Arg synonymous_variant Exon 1 of 6 1 NM_012331.5 ENSP00000313921.4 Q9UJ68-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.98e-7
AC:
1
AN:
1431952
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
712304
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:
30496
American (AMR)
AF:
0.00
AC:
0
AN:
41586
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25244
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35552
South Asian (SAS)
AF:
0.00
AC:
0
AN:
83654
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52908
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
9.11e-7
AC:
1
AN:
1097670
Other (OTH)
AF:
0.00
AC:
0
AN:
59154
⚠️ 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: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
7.5
DANN
Benign
0.81
PhyloP100
0.66
PromoterAI
0.071
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: rs138517353; hg19: chr8-9912092; API