rs1057520200
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PS1_ModeratePM2PP5_Very_Strong
The NM_000273.3(GPR143):āc.2T>Cā(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ā ).
Frequency
Genomes: not found (cov: 24)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
GPR143
NM_000273.3 start_lost
NM_000273.3 start_lost
Scores
9
4
1
Clinical Significance
Conservation
PhyloP100: 8.23
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 20 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_000273.3 (GPR143) was described as [Likely_pathogenic] in ClinVar as 2635351
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-9765816-A-G is Pathogenic according to our data. Variant chrX-9765816-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 377335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-9765816-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR143 | NM_000273.3 | c.2T>C | p.Met1? | start_lost | 1/9 | ENST00000467482.6 | |
GPR143 | XM_005274541.4 | c.2T>C | p.Met1? | start_lost | 1/9 | ||
GPR143 | XM_024452388.2 | c.-2-4990T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR143 | ENST00000467482.6 | c.2T>C | p.Met1? | start_lost | 1/9 | 1 | NM_000273.3 | P1 | |
GPR143 | ENST00000431126.1 | c.-3+304T>C | intron_variant | 3 | |||||
GPR143 | ENST00000447366.5 | c.-2-4990T>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 993827Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 312275
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
993827
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
312275
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GPR143 protein in which other variant(s) (p.Gly84Asp) have been determined to be pathogenic (PMID: 8634705, 11115845, 12868035, 31574285). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 377335). Disruption of the initiator codon has been observed in individual(s) with ocular albinism (PMID: 31106028). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the GPR143 mRNA. The next in-frame methionine is located at codon 85. - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 13, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at M1 (P = 0.0058);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at