GeneBe

chr8-10207815-C-CTTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012331.5(MSRA):​c.143-7_143-5dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 1,156,414 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

MSRA
NM_012331.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSRANM_012331.5 linkc.143-7_143-5dupTTT splice_region_variant, intron_variant Intron 1 of 5 ENST00000317173.9 NP_036463.1 Q9UJ68-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MSRAENST00000317173.9 linkc.143-7_143-5dupTTT splice_region_variant, intron_variant Intron 1 of 5 1 NM_012331.5 ENSP00000313921.4 Q9UJ68-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000432
AC:
50
AN:
1156414
Hom.:
0
Cov.:
0
AF XY:
0.0000536
AC XY:
31
AN XY:
577878
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000761
AC:
2
AN:
26272
American (AMR)
AF:
0.0000581
AC:
2
AN:
34452
Ashkenazi Jewish (ASJ)
AF:
0.0000466
AC:
1
AN:
21466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
32744
South Asian (SAS)
AF:
0.0000436
AC:
3
AN:
68866
European-Finnish (FIN)
AF:
0.0000732
AC:
3
AN:
40964
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4234
European-Non Finnish (NFE)
AF:
0.0000421
AC:
37
AN:
879184
Other (OTH)
AF:
0.0000415
AC:
2
AN:
48232
⚠️ 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: 0.249
Heterozygous variant carriers
0
7
14
22
29
36
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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs77793822; hg19: chr8-10065325; API