rs367576664
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001563.4(IMPG1):c.1519C>T(p.Arg507*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001563.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IMPG1 | NM_001563.4 | c.1519C>T | p.Arg507* | stop_gained | Exon 13 of 17 | ENST00000369950.8 | NP_001554.2 | |
IMPG1 | NM_001282368.2 | c.1285C>T | p.Arg429* | stop_gained | Exon 12 of 16 | NP_001269297.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IMPG1 | ENST00000369950.8 | c.1519C>T | p.Arg507* | stop_gained | Exon 13 of 17 | 1 | NM_001563.4 | ENSP00000358966.3 | ||
IMPG1 | ENST00000611179.4 | c.1285C>T | p.Arg429* | stop_gained | Exon 12 of 16 | 5 | ENSP00000481913.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250894Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135616
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461558Hom.: 1 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727078
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Vitelliform macular dystrophy 4 Pathogenic:1
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not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 162135). This premature translational stop signal has been observed in individual(s) with autosomal recessive macular dystrophy (PMID: 23993198). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs367576664, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg507*) in the IMPG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IMPG1 are known to be pathogenic (PMID: 23993198). -
IMPG1-related disorder Uncertain:1
The IMPG1 c.1519C>T variant is predicted to result in premature protein termination (p.Arg507*). This variant has been reported in the compound heterozygous state in two siblings with vitelliform macular dystrophy (Manes et al. 2013. PubMed ID: 23993198). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. Nonsense variants in IMPG1 are not yet a fully established mechanism of disease. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at