X-9743555-G-T

Position:

• chrX-9743555-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000467482.6(GPR143):​c.767+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,013,890 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000099 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.0000089 (0 hom. 2 hem.)
• Consequence: GPR143 ENST00000467482.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR143	NM_000273.3	c.767+10C>A		intron_variant		ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4	c.767+10C>A		intron_variant			XP_005274598.1
GPR143	XM_024452388.2	c.515+10C>A		intron_variant			XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.767+10C>A		intron_variant		1	NM_000273.3	ENSP00000417161	P1
GPR143	ENST00000447366.5	c.515+10C>A		intron_variant		3		ENSP00000390546
GPR143	ENST00000431126.1			downstream_gene_variant		3		ENSP00000406138

Frequencies

GnomAD3 genomes AF: 0.0000992 AC: 11 AN: 110840 Hom.: 0 Cov.: 22 AF XY: 0.0000604 AC XY: 2 AN XY: 33088

Gnomad AFR AF: 0.000360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000547 AC: 1 AN: 182915 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67399

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000886 AC: 8 AN: 902998 Hom.: 0 Cov.: 17 AF XY: 0.00000760 AC XY: 2 AN XY: 263072

Gnomad4 AFR exome AF: 0.000221

Gnomad4 AMR exome AF: 0.0000572

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: 0.00

Gnomad4 OTH exome AF: 0.0000253

GnomAD4 genome AF: 0.0000992 AC: 11 AN: 110892 Hom.: 0 Cov.: 22 AF XY: 0.0000603 AC XY: 2 AN XY: 33150

Gnomad4 AFR AF: 0.000359

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3788938; hg19: chrX-9711595;