X-9762798-G-C

Variant summary

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

The NM_000273.3(GPR143):c.251-1972C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.82 (26389 hom., 26075 hem., cov: 22)
  • Failed GnomAD Quality Control
• 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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS2: High Homozygotes in GnomAd at 26394 XL gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.251-1972C>G		intron_variant		1	NM_000273.3	P1
GPR143	ENST00000431126.1	c.-2-1972C>G		intron_variant		3
GPR143	ENST00000447366.5	c.-2-1972C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 89749 AN: 109975 Hom.: 26394 Cov.: 22 AF XY: 0.808 AC XY: 26019 AN XY: 32195

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.827

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.799

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.816 AC: 89790 AN: 110028 Hom.: 26389 Cov.: 22 AF XY: 0.808 AC XY: 26075 AN XY: 32258

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.799

Alfa AF: 0.809 Hom.: 6487

Bravo AF: 0.814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.34
Dann	Benign	0.71

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;