X-9725828-C-T

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.1133G>A(p.Ser378Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,206,834 control chromosomes in the GnomAD database, including 1 homozygotes. There are 82 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., 28 hem., cov: 21)
  • Exomes 𝑓: 0.00017 (1 hom. 54 hem.)
• Consequence: GPR143 NM_000273.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.88

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 (MetaRNN=0.009893656).
• BP6: Variant X-9725828-C-T is Benign according to our data. Variant chrX-9725828-C-T is described in ClinVar as [Benign]. Clinvar id is 720640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00097 (107/110366) while in subpopulation AFR AF= 0.0034 (103/30261). AF 95% confidence interval is 0.00287. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 28 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.1133G>A	p.Ser378Asn	missense_variant	9/9	ENST00000467482.6
GPR143	XM_024452388.2	c.881G>A	p.Ser294Asn	missense_variant	9/9
GPR143	XM_005274541.4	c.*108G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.1133G>A	p.Ser378Asn	missense_variant	9/9	1	NM_000273.3	P1
TBL1X	ENST00000647060.1	c.1554+10825C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000952 AC: 105 AN: 110323 Hom.: 0 Cov.: 21 AF XY: 0.000860 AC XY: 28 AN XY: 32549

Gnomad AFR AF: 0.00334

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000968

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: 0.0000378

Gnomad OTH AF: 0.000678

GnomAD3 exomes AF: 0.000371 AC: 67 AN: 180555 Hom.: 0 AF XY: 0.000154 AC XY: 10 AN XY: 65119

Gnomad AFR exome AF: 0.00447

Gnomad AMR exome AF: 0.000257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 183 AN: 1096468 Hom.: 1 Cov.: 29 AF XY: 0.000149 AC XY: 54 AN XY: 361860

Gnomad4 AFR exome AF: 0.00538

Gnomad4 AMR exome AF: 0.000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000951

Gnomad4 OTH exome AF: 0.000456

GnomAD4 genome AF: 0.000970 AC: 107 AN: 110366 Hom.: 0 Cov.: 21 AF XY: 0.000859 AC XY: 28 AN XY: 32602

Gnomad4 AFR AF: 0.00340

Gnomad4 AMR AF: 0.0000967

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000378

Gnomad4 OTH AF: 0.000669

Alfa AF: 0.000144 Hom.: 4

Bravo AF: 0.00113

ESP6500AA AF: 0.00287 AC: 11

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000453 AC: 55

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 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.080
Cadd	Benign	23
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.79	D
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.0099	T
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.60
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.89
MPC		0.059
ClinPred		0.060	T
GERP RS		4.3
Varity_R		0.39
gMVP		0.44

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: rs150992924; hg19: chrX-9693868;