Variant X-9725612-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000273.3(GPR143):c.*134C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 506,144 control chromosomes in the GnomAD database, including 19,753 homozygotes. There are 41,194 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 7896 hom., 11397 hem., cov: 22)

Exomes 𝑓: 0.24 ( 11857 hom. 29797 hem. )

Consequence

GPR143
NM_000273.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.143

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:

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-9725612-G-A is Benign according to our data. Variant chrX-9725612-G-A is described in ClinVar as [Benign]. Clinvar id is 1294751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GPR143	NM_000273.3 linkuse as main transcript	c.*134C>T	3_prime_UTR_variant	9/9	ENST00000467482.6
GPR143	XM_005274541.4 linkuse as main transcript	c.*324C>T	3_prime_UTR_variant	9/9
GPR143	XM_024452388.2 linkuse as main transcript	c.*134C>T	3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6 linkuse as main transcript	c.*134C>T		3_prime_UTR_variant	9/9	1	NM_000273.3	P1
TBL1X	ENST00000647060.1 linkuse as main transcript	c.1554+10609G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

39898

AN:

110264

Hom.:

7879

Cov.:

AF XY:

0.349

AC XY:

11355

AN XY:

32566

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.265

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.238

AC:

94198

AN:

395828

Hom.:

11857

Cov.:

AF XY:

0.231

AC XY:

29797

AN XY:

129124

show subpopulations

Gnomad4 AFR exome

AF:

0.751

Gnomad4 AMR exome

AF:

0.473

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.362

AC:

39957

AN:

110316

Hom.:

7896

Cov.:

AF XY:

0.349

AC XY:

11397

AN XY:

32628

show subpopulations

Gnomad4 AFR

AF:

0.739

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.271

Hom.:

5043

Bravo

AF:

0.410

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.45

DANN

Benign

0.52

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