X-9743555-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000273.3(GPR143):c.767+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,012,845 control chromosomes in the GnomAD database, including 17,349 homozygotes. There are 67,243 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 1385 hom., 5467 hem., cov: 22)

Exomes 𝑓: 0.22 ( 15964 hom. 61776 hem. )

Consequence

GPR143
NM_000273.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.347

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
ocular albinism
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
nystagmus 6, congenital, X-linked
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
X-linked recessive ocular albinism
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

GPR143 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-9743555-G-C is Benign according to our data. Variant chrX-9743555-G-C is described in ClinVar as [Benign]. Clinvar id is 255712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3 link	c.767+10C>G	intron_variant	Intron 6 of 8	ENST00000467482.6	NP_000264.2	P51810
GPR143	NM_001440781.1 link	c.767+10C>G	intron_variant	Intron 6 of 8		NP_001427710.1
GPR143	XM_024452388.2 link	c.515+10C>G	intron_variant	Intron 6 of 8		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR143	ENST00000467482.6 link	c.767+10C>G	intron_variant	Intron 6 of 8	1	NM_000273.3	ENSP00000417161.1	P51810
GPR143	ENST00000447366.5 link	c.515+10C>G	intron_variant	Intron 6 of 7	3		ENSP00000390546.2	H7BZN6
GPR143	ENST00000431126.1 link	c.*10C>G	downstream_gene_variant		3		ENSP00000406138.1	C9J9N1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

18893

AN:

110810

Hom.:

1384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.203

AC:

37159

AN:

182915

AF XY:

0.221

show subpopulations

Gnomad AFR exome

AF:

0.0616

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.222

AC:

200283

AN:

901983

Hom.:

15964

Cov.:

AF XY:

0.235

AC XY:

61776

AN XY:

263049

show subpopulations

African (AFR)

AF:

0.0632

AC:

1430

AN:

22610

American (AMR)

AF:

0.0813

AC:

2844

AN:

34964

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

5115

AN:

18203

East Asian (EAS)

AF:

0.221

AC:

6482

AN:

29338

South Asian (SAS)

AF:

0.324

AC:

16242

AN:

50139

European-Finnish (FIN)

AF:

0.210

AC:

8506

AN:

40411

Middle Eastern (MID)

AF:

0.289

AC:

1075

AN:

3720

European-Non Finnish (NFE)

AF:

0.226

AC:

149940

AN:

663098

Other (OTH)

AF:

0.219

AC:

8649

AN:

39500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5715

11430

17144

22859

28574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.170

AC:

18892

AN:

110862

Hom.:

1385

Cov.:

AF XY:

0.165

AC XY:

5467

AN XY:

33134

show subpopulations

African (AFR)

AF:

0.0619

AC:

1894

AN:

30606

American (AMR)

AF:

0.112

AC:

1162

AN:

10376

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

724

AN:

2629

East Asian (EAS)

AF:

0.228

AC:

795

AN:

3486

South Asian (SAS)

AF:

0.321

AC:

840

AN:

2615

European-Finnish (FIN)

AF:

0.205

AC:

1203

AN:

5857

Middle Eastern (MID)

AF:

0.251

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.223

AC:

11790

AN:

52896

Other (OTH)

AF:

0.177

AC:

266

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

573

1147

1720

2294

2867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.147

Hom.:

1180

Bravo

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ocular albinism, type I

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nystagmus 6, congenital, X-linked

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.83

CADD

Benign

7.1

(source)

DANN

Benign

0.38

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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X-9743555-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over