chrX-9739470-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0210

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:

LOC105373126 (HGNC:):

LOC105373126 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 24. This position FAILED quality control check.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3 link	c.1120+15G>T	intron_variant	Intron 8 of 8	ENST00000467482.6	NP_000264.2	P51810
GPR143	XM_005274541.4 link	c.1120+15G>T	intron_variant	Intron 8 of 8		XP_005274598.1
GPR143	XM_024452388.2 link	c.868+15G>T	intron_variant	Intron 8 of 8		XP_024308156.1
LOC105373126	XR_950507.2 link	n.1620+751C>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR143	ENST00000467482.6 link	c.1120+15G>T	intron_variant	Intron 8 of 8	1	NM_000273.3	ENSP00000417161.1	P51810
TBL1X	ENST00000647060.1 link	c.1555-1312C>A	intron_variant	Intron 15 of 15			ENSP00000495467.1	A0A2R8YFW3
GPR143	ENST00000487206.1 link	n.235+15G>T	intron_variant	Intron 1 of 1	3
GPR143	ENST00000447366.5 link	c.*82G>T	downstream_gene_variant		3		ENSP00000390546.2	H7BZN6

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

112316

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000114

AC:

AN:

166423

AF XY:

0.0000749

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000423

AC:

AN:

1017039

Hom.:

Cov.:

AF XY:

0.0000491

AC XY:

AN XY:

305229

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

AC:

AN:

24872

Gnomad4 AMR exome

AF:

0.000116

AC:

AN:

34487

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

18748

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

29620

Gnomad4 SAS exome

AF:

0.0000390

AC:

AN:

51309

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

39998

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

770658

Gnomad4 Remaining exome

AF:

0.000161

AC:

AN:

43450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000240

AC:

AN:

112316

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34470

show subpopulations

Gnomad4 AFR

AF:

0.000743

AC:

0.000743422

AN:

0.000743422

Gnomad4 AMR

AF:

0.0000942

AC:

0.0000942241

AN:

0.0000942241

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00198

AC:

0.00198282

AN:

0.00198282

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000295

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.72

Mutation Taster

=100/0

polymorphism

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