rs1057518787
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000273.3(GPR143):c.12_36del(p.Leu6GlyfsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 24)
Consequence
GPR143
NM_000273.3 frameshift
NM_000273.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.82
Genes affected
GPR143 (HGNC:20145): (G protein-coupled receptor 143) This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 70 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-9765781-TGGGGCAGCAGAAGGTCCCTAGGCGC-T is Pathogenic according to our data. Variant chrX-9765781-TGGGGCAGCAGAAGGTCCCTAGGCGC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 373941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR143 | NM_000273.3 | c.12_36del | p.Leu6GlyfsTer9 | frameshift_variant | 1/9 | ENST00000467482.6 | |
GPR143 | XM_005274541.4 | c.12_36del | p.Leu6GlyfsTer9 | frameshift_variant | 1/9 | ||
GPR143 | XM_024452388.2 | c.-2-4980_-2-4956del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR143 | ENST00000467482.6 | c.12_36del | p.Leu6GlyfsTer9 | frameshift_variant | 1/9 | 1 | NM_000273.3 | P1 | |
GPR143 | ENST00000431126.1 | c.-3+314_-3+338del | intron_variant | 3 | |||||
GPR143 | ENST00000447366.5 | c.-2-4980_-2-4956del | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ocular albinism, type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Jul 27, 2022 | PVS1 PM2 PM3_Supporting - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 28, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 373941). This variant has not been reported in the literature in individuals affected with GPR143-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu6Glyfs*9) in the GPR143 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GPR143 are known to be pathogenic (PMID: 15965158, 18978956, 19390656, 21541274, 26160353, 28211458). - |
Nystagmus;C0078917:Ocular albinism;C1445953:Reduced eye contact Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Dec 13, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at