rs190174009

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000273.3(GPR143):c.1120+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,125,567 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 74 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 38 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 36 hem. )

Consequence

GPR143
NM_000273.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.421

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hypothyroidism, congenital, nongoitrous, 8
Inheritance: Unknown, XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

TBL1X links:

LOC105373126 (HGNC:):

LOC105373126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-9739469-G-A is Benign according to our data. Variant chrX-9739469-G-A is described in ClinVar as Benign. ClinVar VariationId is 255710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00118 (132/112278) while in subpopulation AFR AF = 0.00423 (131/30984). AF 95% confidence interval is 0.00364. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 38 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000273.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	NM_000273.3	MANE Select	c.1120+16C>T		intron	N/A	NP_000264.2	P51810
	GPR143	NM_001440781.1		c.1120+16C>T		intron	N/A	NP_001427710.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPR143	ENST00000467482.6	TSL:1 MANE Select	c.1120+16C>T	intron	N/A	ENSP00000417161.1	P51810
TBL1X	ENST00000647060.1		c.1555-1313G>A	intron	N/A	ENSP00000495467.1	A0A2R8YFW3
GPR143	ENST00000929114.1		c.1204+16C>T	intron	N/A	ENSP00000599173.1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

132

AN:

112228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00424

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

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:

0.00

GnomAD2 exomes

AF:

0.000393

AC:

AN:

165422

AF XY:

0.000209

show subpopulations

Gnomad AFR exome

AF:

0.00512

Gnomad AMR exome

AF:

0.0000771

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

142

AN:

1013289

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

302293

show subpopulations

African (AFR)

AF:

0.00503

AC:

125

AN:

24840

American (AMR)

AF:

0.0000581

AC:

AN:

34431

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18723

East Asian (EAS)

AF:

0.00

AC:

AN:

29601

South Asian (SAS)

AF:

0.00

AC:

AN:

51167

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39939

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3886

European-Non Finnish (NFE)

AF:

0.00000130

AC:

AN:

767386

Other (OTH)

AF:

0.000323

AC:

AN:

43316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00118

AC:

132

AN:

112278

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

34454

show subpopulations

African (AFR)

AF:

0.00423

AC:

131

AN:

30984

American (AMR)

AF:

0.0000942

AC:

AN:

10617

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53214

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00145

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

(source)

DANN

Benign

0.75

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over