Variant rs58933950 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000273.3(GPR143):c.455G>A(p.Ser152Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.7e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

GPR143
NM_000273.3 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1O:1

Conservation

PhyloP100: 6.79

Variant links:

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]

GPR143 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GPR143	NM_000273.3 linkuse as main transcript	c.455G>A	p.Ser152Asn	missense_variant, splice_region_variant	3/9	ENST00000467482.6
GPR143	XM_005274541.4 linkuse as main transcript	c.455G>A	p.Ser152Asn	missense_variant, splice_region_variant	3/9
GPR143	XM_024452388.2 linkuse as main transcript	c.203G>A	p.Ser68Asn	missense_variant, splice_region_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPR143	ENST00000467482.6 linkuse as main transcript	c.455G>A	p.Ser152Asn	missense_variant, splice_region_variant	3/9	1	NM_000273.3	P1
GPR143	ENST00000447366.5 linkuse as main transcript	c.203G>A	p.Ser68Asn	missense_variant, splice_region_variant	3/8	3
GPR143	ENST00000431126.1 linkuse as main transcript	c.203G>A	p.Ser68Asn	missense_variant, splice_region_variant	3/6	3
GPR143	ENST00000480178.1 linkuse as main transcript	n.63G>A		splice_region_variant, non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.66e-7

AC:

AN:

1035692

Hom.:

Cov.:

AF XY:

0.00000316

AC XY:

AN XY:

316546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000127

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ocular albinism, type I

Pathogenic:1Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 01, 1998	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Mar 25, 2024	- -

not provided

Other:1

not provided, no classification provided

literature only

Retina International

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

D;.;D

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

T;T;T

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

A;A

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

N;.;N

REVEL

Pathogenic

0.69

Sift

Benign

0.077

T;.;D

Sift4G

Uncertain

0.016

D;D;.

Polyphen

0.97

D;.;.

Vest4

0.87

MutPred

0.72

Gain of relative solvent accessibility (P = 0.0215);.;.;

MVP

0.90

MPC

0.065

ClinPred

0.97

GERP RS

4.7

Varity_R

0.40

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

1.0

SpliceAI score (max)

0.78

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.78

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over