X-9760811-G-T

Variant names:

• chrX-9760811-G-T
• NM_000273.3:c.266C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000273.3(GPR143):​c.266C>A​(p.Ser89Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000992 in 1,007,597 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.9e-7 (0 hom. 1 hem.)
• Consequence: GPR143 NM_000273.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.55

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 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3	c.266C>A	p.Ser89Tyr	missense_variant	Exon 2 of 9	ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4	c.266C>A	p.Ser89Tyr	missense_variant	Exon 2 of 9		XP_005274598.1
GPR143	XM_024452388.2	c.14C>A	p.Ser5Tyr	missense_variant	Exon 2 of 9		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.266C>A	p.Ser89Tyr	missense_variant	Exon 2 of 9	1	NM_000273.3	ENSP00000417161.1
GPR143	ENST00000447366.5	c.14C>A	p.Ser5Tyr	missense_variant	Exon 2 of 8	3		ENSP00000390546.2
GPR143	ENST00000431126.1	c.14C>A	p.Ser5Tyr	missense_variant	Exon 2 of 6	3		ENSP00000406138.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.92e-7 AC: 1 AN: 1007597 Hom.: 0 Cov.: 22 AF XY: 0.00000344 AC XY: 1 AN XY: 290929

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: 0.00000131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.98	D;.;D
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.8	D;.;D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.91
MutPred		0.83		Loss of sheet (P = 0.0104);.;.;
MVP		0.96
MPC		0.31
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.83
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-9728851;