X-9762798-G-C

Variant names:

• chrX-9762798-G-C
• rs2521667
• NM_000273.3:c.251-1972C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3	c.251-1972C>G		intron_variant	Intron 1 of 8	ENST00000467482.6	NP_000264.2
GPR143	NM_001440781.1	c.251-1972C>G		intron_variant	Intron 1 of 8		NP_001427710.1
GPR143	XM_024452388.2	c.-2-1972C>G		intron_variant	Intron 1 of 8		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.251-1972C>G		intron_variant	Intron 1 of 8	1	NM_000273.3	ENSP00000417161.1
GPR143	ENST00000447366.5	c.-2-1972C>G		intron_variant	Intron 1 of 7	3		ENSP00000390546.2
GPR143	ENST00000431126.1	c.-2-1972C>G		intron_variant	Intron 1 of 5	3		ENSP00000406138.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 89749 AN: 109975 Hom.: 26394 Cov.: 22

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

African (AFR) AF: 0.911 AC: 27574 AN: 30255

American (AMR) AF: 0.750 AC: 7671 AN: 10234

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 2286 AN: 2635

East Asian (EAS) AF: 0.495 AC: 1711 AN: 3454

South Asian (SAS) AF: 0.651 AC: 1681 AN: 2582

European-Finnish (FIN) AF: 0.807 AC: 4634 AN: 5739

Middle Eastern (MID) AF: 0.815 AC: 176 AN: 216

European-Non Finnish (NFE) AF: 0.802 AC: 42272 AN: 52726

Other (OTH) AF: 0.799 AC: 1205 AN: 1508

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2521667; hg19: chrX-9730838;