rs61733440

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0680

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GPR143	NM_000273.3 linkuse as main transcript	c.570C>T	p.His190=	synonymous_variant	5/9	ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4 linkuse as main transcript	c.570C>T	p.His190=	synonymous_variant	5/9		XP_005274598.1
GPR143	XM_024452388.2 linkuse as main transcript	c.318C>T	p.His106=	synonymous_variant	5/9		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GPR143	ENST00000467482.6 linkuse as main transcript	c.570C>T	p.His190=	synonymous_variant	5/9	1	NM_000273.3	ENSP00000417161	P1
GPR143	ENST00000447366.5 linkuse as main transcript	c.318C>T	p.His106=	synonymous_variant	5/8	3		ENSP00000390546
GPR143	ENST00000431126.1 linkuse as main transcript	c.318C>T	p.His106=	synonymous_variant	5/6	3		ENSP00000406138

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

577

AN:

111840

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

132

AN XY:

34002

show subpopulations

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.:

AF XY:

0.000870

AC XY:

AN XY:

67795

show subpopulations

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.:

Cov.:

AF XY:

0.000379

AC XY:

130

AN XY:

343433

show subpopulations

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.:

Cov.:

AF XY:

0.00390

AC XY:

133

AN XY:

34067

show subpopulations

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.:

Bravo

AF:

0.00623

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 10, 2015	- -
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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over