chrX-9739469-G-A

Position:

chrX-9739469-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000273.3(GPR143):c.1120+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,125,567 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 74 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 38 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 36 hem. )

Consequence

GPR143
NM_000273.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.421

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-9739469-G-A is Benign according to our data. Variant chrX-9739469-G-A is described in ClinVar as [Benign]. Clinvar id is 255710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00118 (132/112278) while in subpopulation AFR AF= 0.00423 (131/30984). AF 95% confidence interval is 0.00364. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 38 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GPR143	NM_000273.3 linkuse as main transcript	c.1120+16C>T	intron_variant	ENST00000467482.6
LOC105373126	XR_950507.2 linkuse as main transcript	n.1620+750G>A	intron_variant, non_coding_transcript_variant
GPR143	XM_005274541.4 linkuse as main transcript	c.1120+16C>T	intron_variant
GPR143	XM_024452388.2 linkuse as main transcript	c.868+16C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GPR143	ENST00000467482.6 linkuse as main transcript	c.1120+16C>T	intron_variant	1	NM_000273.3	P1
TBL1X	ENST00000647060.1 linkuse as main transcript	c.1555-1313G>A	intron_variant
GPR143	ENST00000487206.1 linkuse as main transcript	n.235+16C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

132

AN:

112228

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

34394

show subpopulations

Gnomad AFR

AF:

0.00424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000393

AC:

AN:

165422

Hom.:

AF XY:

0.000209

AC XY:

AN XY:

52728

show subpopulations

Gnomad AFR exome

AF:

0.00512

Gnomad AMR exome

AF:

0.0000771

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:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

142

AN:

1013289

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

302293

show subpopulations

Gnomad4 AFR exome

AF:

0.00503

Gnomad4 AMR exome

AF:

0.0000581

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:

0.00000130

Gnomad4 OTH exome

AF:

0.000323

GnomAD4 genome

AF:

0.00118

AC:

132

AN:

112278

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

34454

show subpopulations

Gnomad4 AFR

AF:

0.00423

Gnomad4 AMR

AF:

0.0000942

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00145

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

DANN

Benign

0.75

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