X-9725612-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.143

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.362 AC: 39898 AN: 110264 Hom.: 7879 Cov.: 22 AF XY: 0.349 AC XY: 11355 AN XY: 32566

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.: 5 AF XY: 0.231 AC XY: 29797 AN XY: 129124

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.: 22 AF XY: 0.349 AC XY: 11397 AN XY: 32628

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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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

Other links and lift over

dbSNP: rs3044; hg19: chrX-9693652; COSMIC: COSV66632069;