rs2521667

Positions:

• chrX-9762798-G-A
• chrX-9762798-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000273.3(GPR143):​c.251-1972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
• Consequence: GPR143 NM_000273.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR143	NM_000273.3	c.251-1972C>T		intron_variant		ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4	c.251-1972C>T		intron_variant			XP_005274598.1
GPR143	XM_024452388.2	c.-2-1972C>T		intron_variant			XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.251-1972C>T		intron_variant		1	NM_000273.3	ENSP00000417161.1
GPR143	ENST00000447366.5	c.-2-1972C>T		intron_variant		3		ENSP00000390546.2
GPR143	ENST00000431126.1	c.-2-1972C>T		intron_variant		3		ENSP00000406138.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2521667; hg19: chrX-9730838;