chrX-9759416-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_000273.3(GPR143):c.371A>G(p.Gln124Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000353 in 1,177,095 control chromosomes in the GnomAD database, including 1 homozygotes. There are 121 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00036 ( 1 hom. 114 hem. )

Consequence

GPR143
NM_000273.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 6.88

Publications

3 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: Benign. The variant received -18 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 12 uncertain in NM_000273.3

BP4

Computational evidence support a benign effect (MetaRNN=0.04116428).

BP6

Variant X-9759416-T-C is Benign according to our data. Variant chrX-9759416-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 98632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000269 (30/111560) while in subpopulation AMR AF = 0.000578 (6/10372). AF 95% confidence interval is 0.000251. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR143	NM_000273.3 link	c.371A>G	p.Gln124Arg	missense_variant	Exon 3 of 9	ENST00000467482.6	NP_000264.2	P51810
GPR143	NM_001440781.1 link	c.371A>G	p.Gln124Arg	missense_variant	Exon 3 of 9		NP_001427710.1
GPR143	XM_024452388.2 link	c.119A>G	p.Gln40Arg	missense_variant	Exon 3 of 9		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR143	ENST00000467482.6 link	c.371A>G	p.Gln124Arg	missense_variant	Exon 3 of 9	1	NM_000273.3	ENSP00000417161.1	P51810
GPR143	ENST00000447366.5 link	c.119A>G	p.Gln40Arg	missense_variant	Exon 3 of 8	3		ENSP00000390546.2	H7BZN6
GPR143	ENST00000431126.1 link	c.119A>G	p.Gln40Arg	missense_variant	Exon 3 of 6	3		ENSP00000406138.1	C9J9N1
GPR143	ENST00000480178.1 link	n.-22A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

111560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000578

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:

0.000357

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000519

AC:

AN:

163845

AF XY:

0.000343

show subpopulations

Gnomad AFR exome

AF:

0.0000866

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.000361

AC:

385

AN:

1065535

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

114

AN XY:

334509

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25667

American (AMR)

AF:

0.00178

AC:

AN:

34228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19073

East Asian (EAS)

AF:

0.00

AC:

AN:

29643

South Asian (SAS)

AF:

0.00

AC:

AN:

51824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4052

European-Non Finnish (NFE)

AF:

0.000386

AC:

315

AN:

816063

Other (OTH)

AF:

0.000200

AC:

AN:

45029

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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

100

<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:

0.000269

AC:

AN:

111560

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33748

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30656

American (AMR)

AF:

0.000578

AC:

AN:

10372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000357

AC:

AN:

53167

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.000345

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000480

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 28, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 17, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ocular albinism, type I

Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.70

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

D;.;D

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

M;.;.

PhyloP100

6.9

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.9

D;.;D

REVEL

Pathogenic

0.93

Sift

Uncertain

0.0070

D;.;D

Sift4G

Uncertain

0.0060

D;D;.

Polyphen

0.95

P;.;.

Vest4

0.90

MVP

1.0

MPC

0.046

ClinPred

0.065

GERP RS

4.7

Varity_R

0.76

gMVP

0.90

Mutation Taster

=64/36

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over