rs62635018

chrX-9765714-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_Strong PP5

The NM_000273.3(GPR143):c.104G>A(p.Gly35Asp) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G35V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR143 NM_000273.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 4.20

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 Uncertain_significance. Variant got 5 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949
• PP5: Variant X-9765714-C-T is Pathogenic according to our data. Variant chrX-9765714-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 10521.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.104G>A	p.Gly35Asp	missense_variant	1/9	ENST00000467482.6
GPR143	XM_005274541.4	c.104G>A	p.Gly35Asp	missense_variant	1/9
GPR143	XM_024452388.2	c.-2-4888G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.104G>A	p.Gly35Asp	missense_variant	1/9	1	NM_000273.3	P1
GPR143	ENST00000431126.1	c.-3+406G>A		intron_variant		3
GPR143	ENST00000447366.5	c.-2-4888G>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1003691 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 323697

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.: 25

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ocular albinism, type I Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1998

- -

not provided Other:1

not provided, no classification provided

literature only

Retina International

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.63
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	A;A
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.84
Sift	Benign	0.098	T
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.77		Gain of relative solvent accessibility (P = 0.0023);
MVP		1.0
MPC		0.31
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.42
gMVP		0.86

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: rs62635018; hg19: chrX-9733754;