rs5934683

Variant names:

• chrX-9783434-T-C
• rs5934683
• ENST00000447366.5:c.-3+2808A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• ocular albinism

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• nystagmus 6, congenital, X-linked

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• X-linked recessive ocular albinism

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000447366.5	c.-3+2808A>G		intron_variant	Intron 1 of 7	3		ENSP00000390546.2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 55165 AN: 110207 Hom.: 11193 Cov.: 22

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

African (AFR) AF: 0.263 AC: 7980 AN: 30375

American (AMR) AF: 0.442 AC: 4579 AN: 10359

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 1567 AN: 2627

East Asian (EAS) AF: 0.173 AC: 602 AN: 3472

South Asian (SAS) AF: 0.403 AC: 1046 AN: 2593

European-Finnish (FIN) AF: 0.584 AC: 3340 AN: 5718

Middle Eastern (MID) AF: 0.505 AC: 109 AN: 216

European-Non Finnish (NFE) AF: 0.658 AC: 34661 AN: 52702

Other (OTH) AF: 0.502 AC: 762 AN: 1519

Alfa AF: 0.590 Hom.: 77021

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
PhyloP100		0.033

Splicing

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

Other links and lift over

dbSNP: rs5934683; hg19: chrX-9751474;