X-9739481-T-C

Position:

chrX-9739481-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP6_ModerateBS1BS2

The NM_000273.3(GPR143):c.1120+4A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0014 in 1,175,233 control chromosomes in the GnomAD database, including 10 homozygotes. There are 447 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 3 hom., 226 hem., cov: 23)

Exomes 𝑓: 0.00081 ( 7 hom. 221 hem. )

Consequence

GPR143
NM_000273.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.9929

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 5.02

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:

LOC105373126 (HGNC:):

LOC105373126 links:

TBL1X (HGNC:11585): (transducin beta like 1 X-linked) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein. This gene is located adjacent to the ocular albinism gene and it is thought to be involved in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype. Four transcript variants encoding two different isoforms have been found for this gene. This gene is highly similar to the Y chromosome TBL1Y gene. [provided by RefSeq, Nov 2008]

TBL1X links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

BP6

Variant X-9739481-T-C is Benign according to our data. Variant chrX-9739481-T-C is described in ClinVar as [Benign]. Clinvar id is 719864.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-9739481-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.007 (785/112146) while in subpopulation AFR AF= 0.024 (742/30902). AF 95% confidence interval is 0.0226. There are 3 homozygotes in gnomad4. There are 226 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	Effect	MANE
GPR143	NM_000273.3 linkuse as main transcript	c.1120+4A>G	splice_donor_region_variant, intron_variant	ENST00000467482.6
LOC105373126	XR_950507.2 linkuse as main transcript	n.1620+762T>C	intron_variant, non_coding_transcript_variant
GPR143	XM_005274541.4 linkuse as main transcript	c.1120+4A>G	splice_donor_region_variant, intron_variant
GPR143	XM_024452388.2 linkuse as main transcript	c.868+4A>G	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GPR143	ENST00000467482.6 linkuse as main transcript	c.1120+4A>G	splice_donor_region_variant, intron_variant	1	NM_000273.3	P1
TBL1X	ENST00000647060.1 linkuse as main transcript	c.1555-1301T>C	intron_variant
GPR143	ENST00000487206.1 linkuse as main transcript	n.235+4A>G	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

781

AN:

112091

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

225

AN XY:

34273

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00293

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00330

GnomAD3 exomes

AF:

0.00222

AC:

383

AN:

172678

Hom.:

AF XY:

0.00136

AC XY:

AN XY:

58130

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000572

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000131

Gnomad OTH exome

AF:

0.000931

GnomAD4 exome

AF:

0.000814

AC:

865

AN:

1063087

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

221

AN XY:

334511

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000334

Gnomad4 SAS exome

AF:

0.0000380

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000481

Gnomad4 OTH exome

AF:

0.00173

GnomAD4 genome

AF:

0.00700

AC:

785

AN:

112146

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

226

AN XY:

34338

show subpopulations

Gnomad4 AFR

AF:

0.0240

Gnomad4 AMR

AF:

0.00292

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:

0.00392

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00793

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.50

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.50

Position offset: -20

DS_DL_spliceai

0.28

Position offset: 4

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