Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The ENST00000467482.6(GPR143):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GPR143
ENST00000467482.6 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 8.23

Publications

1 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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
ocular albinism
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
nystagmus 6, congenital, X-linked
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
X-linked recessive ocular albinism
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

GPR143 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 33 pathogenic variants. Next in-frame start position is after 85 codons. Genomic position: 9760824. Lost 0.208 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-9765816-A-G is Pathogenic according to our data. Variant chrX-9765816-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 377335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467482.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	NM_000273.3	MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 9	NP_000264.2
	GPR143	NM_001440781.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 9	NP_001427710.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GPR143	ENST00000467482.6	TSL:1 MANE Select	c.2T>C	p.Met1?	start_lost	Exon 1 of 9	ENSP00000417161.1
GPR143	ENST00000447366.5	TSL:3	c.-2-4990T>C		intron	N/A	ENSP00000390546.2
GPR143	ENST00000431126.1	TSL:3	c.-3+304T>C		intron	N/A	ENSP00000406138.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

993827

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

312275

African (AFR)

AF:

0.00

AC:

AN:

21397

American (AMR)

AF:

0.00

AC:

AN:

23302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16710

East Asian (EAS)

AF:

0.00

AC:

AN:

22967

South Asian (SAS)

AF:

0.00

AC:

AN:

43871

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3713

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

793984

Other (OTH)

AF:

0.00

AC:

AN:

41989

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.70

BayesDel_noAF

Pathogenic

0.80

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

1.1

PhyloP100

8.2

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.66

Gain of glycosylation at M1 (P = 0.0058)

MVP

0.99

ClinPred

0.99

GERP RS

4.3

PromoterAI

-0.057

Neutral

(source)

Varity_R

0.92

gMVP

0.84

Mutation Taster

=24/176

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1057520200

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over