Genetic Variant NM_000273.3:c.360+13C>G (chrX-9760704-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000273.3(GPR143):c.360+13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 975,278 control chromosomes in the GnomAD database, including 2,722 homozygotes. There are 22,440 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 382 hom., 2592 hem., cov: 22)

Exomes 𝑓: 0.082 ( 2340 hom. 19848 hem. )

Consequence

GPR143
NM_000273.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.174

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-9760704-G-C is Benign according to our data. Variant chrX-9760704-G-C is described in ClinVar as [Benign]. Clinvar id is 98629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3 link	c.360+13C>G	intron_variant	Intron 2 of 8	ENST00000467482.6	NP_000264.2	P51810
GPR143	XM_005274541.4 link	c.360+13C>G	intron_variant	Intron 2 of 8		XP_005274598.1
GPR143	XM_024452388.2 link	c.108+13C>G	intron_variant	Intron 2 of 8		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR143	ENST00000467482.6 link	c.360+13C>G	intron_variant	Intron 2 of 8	1	NM_000273.3	ENSP00000417161.1	P51810
GPR143	ENST00000447366.5 link	c.108+13C>G	intron_variant	Intron 2 of 7	3		ENSP00000390546.2	H7BZN6
GPR143	ENST00000431126.1 link	c.108+13C>G	intron_variant	Intron 2 of 5	3		ENSP00000406138.1	C9J9N1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

9778

AN:

110653

Hom.:

383

Cov.:

AF XY:

0.0787

AC XY:

2589

AN XY:

32895

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0162

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0398

Gnomad SAS

AF:

0.0322

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.0979

Gnomad NFE

AF:

0.0857

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0740

AC:

11500

AN:

155426

Hom.:

366

AF XY:

0.0695

AC XY:

3329

AN XY:

47914

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0447

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.0366

Gnomad SAS exome

AF:

0.0297

Gnomad FIN exome

AF:

0.0757

Gnomad NFE exome

AF:

0.0866

Gnomad OTH exome

AF:

0.0869

GnomAD4 exome

AF:

0.0823

AC:

71122

AN:

864572

Hom.:

2340

Cov.:

AF XY:

0.0810

AC XY:

19848

AN XY:

245168

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.0502

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.0333

Gnomad4 SAS exome

AF:

0.0298

Gnomad4 FIN exome

AF:

0.0763

Gnomad4 NFE exome

AF:

0.0876

Gnomad4 OTH exome

AF:

0.0854

GnomAD4 genome

AF:

0.0883

AC:

9771

AN:

110706

Hom.:

382

Cov.:

AF XY:

0.0786

AC XY:

2592

AN XY:

32958

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0635

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0399

Gnomad4 SAS

AF:

0.0319

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0856

Gnomad4 OTH

AF:

0.0985

Alfa

AF:

0.0564

Hom.:

423

Bravo

AF:

0.0921

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Sep 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retina International

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.41

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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