rs5934683

Positions:

• chrX-9783434-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000447366.5(GPR143):​c.-3+2808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 110,259 control chromosomes in the GnomAD database, including 11,192 homozygotes. There are 16,013 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (11192 hom., 16013 hem., cov: 22)
• Consequence: GPR143 ENST00000447366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000447366.5	c.-3+2808A>G		intron_variant		3		ENSP00000390546

Frequencies

GnomAD3 genomes AF: 0.501 AC: 55165 AN: 110207 Hom.: 11193 Cov.: 22 AF XY: 0.492 AC XY: 16009 AN XY: 32515

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.511

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 55157 AN: 110259 Hom.: 11192 Cov.: 22 AF XY: 0.492 AC XY: 16013 AN XY: 32577

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.502

Alfa AF: 0.626 Hom.: 60435

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5934683; hg19: chrX-9751474;