rs755116516
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The ENST00000396463.7(WRAP53):βc.1564delβ(p.Ala522ArgfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000591 in 1,607,406 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. G520G) has been classified as Likely benign.
Frequency
Consequence
ENST00000396463.7 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WRAP53 | NM_001143992.2 | c.1564del | p.Ala522ArgfsTer26 | frameshift_variant | 11/11 | ENST00000396463.7 | NP_001137464.1 | |
WRAP53 | NM_001143990.2 | c.1564del | p.Ala522ArgfsTer26 | frameshift_variant | 11/11 | NP_001137462.1 | ||
WRAP53 | NM_001143991.2 | c.1564del | p.Ala522ArgfsTer26 | frameshift_variant | 11/11 | NP_001137463.1 | ||
WRAP53 | NM_018081.2 | c.1564del | p.Ala522ArgfsTer26 | frameshift_variant | 10/10 | NP_060551.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WRAP53 | ENST00000396463.7 | c.1564del | p.Ala522ArgfsTer26 | frameshift_variant | 11/11 | 1 | NM_001143992.2 | ENSP00000379727 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000267 AC: 4AN: 150064Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000100 AC: 25AN: 249660Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135262
GnomAD4 exome AF: 0.0000624 AC: 91AN: 1457342Hom.: 1 Cov.: 34 AF XY: 0.0000593 AC XY: 43AN XY: 725042
GnomAD4 genome AF: 0.0000267 AC: 4AN: 150064Hom.: 0 Cov.: 31 AF XY: 0.0000410 AC XY: 3AN XY: 73228
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 28, 2022 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 31, 2022 | This sequence change creates a premature translational stop signal (p.Ala522Argfs*26) in the WRAP53 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the WRAP53 protein. This variant is present in population databases (rs755116516, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with WRAP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 225516). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | research | Center of Medical Genetics and Primary Health Care | Apr 08, 2020 | ACMG Guidelines 2015 criteria PP3 Pathogenic Supporting: 1 pathogenic prediction from GERP vs no benign predictions. BS1 Benign Strong: GnomAD exomes East Asian allele frequency = 0.0012 > 0.000528 derived from the 60 clinically reported variants in gene WRAP53 of which 2 PATH, 25 VUS and 33 BEN. Therefore, this variant was classified as a Variant of Unknown Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at