rs61733440

chrX-9746132-G-AchrX-9746132-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000273.3(GPR143):c.570C>T(p.His190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000988 in 1,187,424 control chromosomes in the GnomAD database, including 7 homozygotes. There are 263 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (3 hom., 133 hem., cov: 23)
  • Exomes 𝑓: 0.00055 (4 hom. 130 hem.)
• Consequence: GPR143 NM_000273.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0680

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-9746132-G-A is Benign according to our data. Variant chrX-9746132-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-9746132-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00517 (579/111895) while in subpopulation AFR AF= 0.0175 (540/30829). AF 95% confidence interval is 0.0163. There are 3 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.570C>T	p.His190=	synonymous_variant	5/9	ENST00000467482.6
GPR143	XM_005274541.4	c.570C>T	p.His190=	synonymous_variant	5/9
GPR143	XM_024452388.2	c.318C>T	p.His106=	synonymous_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.570C>T	p.His190=	synonymous_variant	5/9	1	NM_000273.3	P1
GPR143	ENST00000447366.5	c.318C>T	p.His106=	synonymous_variant	5/8	3
GPR143	ENST00000431126.1	c.318C>T	p.His106=	synonymous_variant	5/6	3

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 577 AN: 111840 Hom.: 3 Cov.: 23 AF XY: 0.00388 AC XY: 132 AN XY: 34002

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00793

GnomAD3 exomes AF: 0.00156 AC: 286 AN: 183341 Hom.: 3 AF XY: 0.000870 AC XY: 59 AN XY: 67795

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.00106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000244

Gnomad OTH exome AF: 0.00155

GnomAD4 exome AF: 0.000552 AC: 594 AN: 1075529 Hom.: 4 Cov.: 28 AF XY: 0.000379 AC XY: 130 AN XY: 343433

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.00105

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: 0.0000146

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.00517 AC: 579 AN: 111895 Hom.: 3 Cov.: 23 AF XY: 0.00390 AC XY: 133 AN XY: 34067

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00238

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.00783

Alfa AF: 0.000304 Hom.: 1

Bravo AF: 0.00623

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 10, 2015	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.12
Dann	Benign	0.88

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: rs61733440; hg19: chrX-9714172;