NM_001029883.3:c.947delA
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001029883.3(PCARE):c.947delA(p.Asn316MetfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001029883.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCARE | NM_001029883.3 | c.947delA | p.Asn316MetfsTer7 | frameshift_variant | Exon 1 of 2 | ENST00000331664.6 | NP_001025054.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152018Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249544Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135382
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461860Hom.: 0 Cov.: 37 AF XY: 0.0000206 AC XY: 15AN XY: 727228
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74260
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Asn316Metfs*7) in the PCARE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCARE are known to be pathogenic (PMID: 20398886, 24339724, 26496393). This variant is present in population databases (rs779886453, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 20398884). It has also been observed to segregate with disease in related individuals. This variant is also known as c.946 del; p.Asn237MetfsX5. ClinVar contains an entry for this variant (Variation ID: 103). For these reasons, this variant has been classified as Pathogenic. -
Retinitis pigmentosa 54 Pathogenic:1
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Stargardt disease Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at