Genetic Variant GPR143:p.His190Gln (chrX-9746132-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000273.3(GPR143):c.570C>G(p.His190Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 111,840 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H190H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Consequence

GPR143
NM_000273.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.894

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	NM_000273.3	MANE Select	c.570C>G	p.His190Gln	missense	Exon 5 of 9	NP_000264.2
	GPR143	NM_001440781.1		c.570C>G	p.His190Gln	missense	Exon 5 of 9	NP_001427710.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GPR143	ENST00000467482.6	TSL:1 MANE Select	c.570C>G	p.His190Gln	missense	Exon 5 of 9	ENSP00000417161.1
GPR143	ENST00000929114.1		c.654C>G	p.His218Gln	missense	Exon 6 of 10	ENSP00000599173.1
GPR143	ENST00000929113.1		c.570C>G	p.His190Gln	missense	Exon 5 of 9	ENSP00000599172.1

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111840

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30759

American (AMR)

AF:

0.0000954

AC:

AN:

10483

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00

AC:

AN:

2673

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6081

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53203

Other (OTH)

AF:

0.00

AC:

AN:

1513

Age Distribution

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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

8.9

(source)

DANN

Benign

0.95

DEOGEN2

Pathogenic

0.95

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.092

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.5

PhyloP100

0.068

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.4

REVEL

Pathogenic

0.66

Sift

Benign

0.034

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MutPred

0.81

Gain of helix (P = 0.062)

MVP

0.94

MPC

0.20

ClinPred

0.98

GERP RS

-6.7

Varity_R

0.47

gMVP

0.71

Mutation Taster

=71/29

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over