X-9739470-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000273.3(GPR143):c.1120+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,129,355 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., 5 hem., cov: 24)
  • Exomes 𝑓: 0.000042 (0 hom. 15 hem.)
• Consequence: GPR143 NM_000273.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

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]

LOC105373126 (HGNC:):

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=-0.83).
• BP6: Variant X-9739470-C-A is Benign according to our data. Variant chrX-9739470-C-A is described in ClinVar as [Benign]. Clinvar id is 1165936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00024 (27/112316) while in subpopulation AFR AF= 0.000743 (23/30938). AF 95% confidence interval is 0.000507. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.1120+15G>T		intron_variant		ENST00000467482.6
LOC105373126	XR_950507.2	n.1620+751C>A		intron_variant, non_coding_transcript_variant
GPR143	XM_005274541.4	c.1120+15G>T		intron_variant
GPR143	XM_024452388.2	c.868+15G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.1120+15G>T		intron_variant		1	NM_000273.3	P1
TBL1X	ENST00000647060.1	c.1555-1312C>A		intron_variant
GPR143	ENST00000487206.1	n.235+15G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000240 AC: 27 AN: 112316 Hom.: 0 Cov.: 24 AF XY: 0.000145 AC XY: 5 AN XY: 34470

Gnomad AFR AF: 0.000743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000942

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: 0.00198

GnomAD3 exomes AF: 0.000114 AC: 19 AN: 166423 Hom.: 0 AF XY: 0.0000749 AC XY: 4 AN XY: 53437

Gnomad AFR exome AF: 0.00132

Gnomad AMR exome AF: 0.000115

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000423 AC: 43 AN: 1017039 Hom.: 0 Cov.: 22 AF XY: 0.0000491 AC XY: 15 AN XY: 305229

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.000116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000390

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000161

GnomAD4 genome AF: 0.000240 AC: 27 AN: 112316 Hom.: 0 Cov.: 24 AF XY: 0.000145 AC XY: 5 AN XY: 34470

Gnomad4 AFR AF: 0.000743

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: 0.00198

Bravo AF: 0.000295

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

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.1
Dann	Benign	0.72

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: rs368826221; hg19: chrX-9707510;