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.Arg507Ter) 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
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 1 hom. )
Consequence
IMPG1
NM_001563.4 stop_gained
NM_001563.4 stop_gained
Scores
1
1
5
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
IMPG1 (HGNC:6055): (interphotoreceptor matrix proteoglycan 1) This gene encodes a protein that is a major component of the retinal interphotoreceptor matrix. The encoded protein is a proteoglycan that is thought to play a role in maintaining viability of photoreceptor cells and in adhesion of the neural retina to the retinal pigment epithelium. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 6-75950867-G-A is Pathogenic according to our data. Variant chr6-75950867-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 162135.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-75950867-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMPG1 | NM_001563.4 | c.1519C>T | p.Arg507Ter | stop_gained | 13/17 | ENST00000369950.8 | |
IMPG1 | NM_001282368.2 | c.1285C>T | p.Arg429Ter | stop_gained | 12/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMPG1 | ENST00000369950.8 | c.1519C>T | p.Arg507Ter | stop_gained | 13/17 | 1 | NM_001563.4 | P2 | |
IMPG1 | ENST00000611179.4 | c.1285C>T | p.Arg429Ter | stop_gained | 12/16 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250894Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135616
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461558Hom.: 1 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727078
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Vitelliform macular dystrophy 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 05, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | 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). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;N
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at