X-9741444-T-C

Variant names:

• chrX-9741444-T-C
• rs62635042
• NM_000273.3:c.779A>G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000273.3(GPR143):​c.779A>G​(p.Asn260Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N260I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR143 NM_000273.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.80

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_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979
• PP5: Variant X-9741444-T-C is Pathogenic according to our data. Variant chrX-9741444-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438187.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3	c.779A>G	p.Asn260Ser	missense_variant	Exon 7 of 9	ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4	c.779A>G	p.Asn260Ser	missense_variant	Exon 7 of 9		XP_005274598.1
GPR143	XM_024452388.2	c.527A>G	p.Asn176Ser	missense_variant	Exon 7 of 9		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.779A>G	p.Asn260Ser	missense_variant	Exon 7 of 9	1	NM_000273.3	ENSP00000417161.1
GPR143	ENST00000447366.5	c.527A>G	p.Asn176Ser	missense_variant	Exon 7 of 8	3		ENSP00000390546.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 923615 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 251549

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Albinism Pathogenic:1

Jan 01, 2015

NIHR Bioresource Rare Diseases, University of Cambridge

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.98	D;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.71	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.3	D;.
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;.
Vest4		0.80
MutPred		0.88		Gain of relative solvent accessibility (P = 0.09);.;
MVP		0.99
MPC		0.26
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.86
gMVP		0.95

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: rs62635042; hg19: chrX-9709484;