rs376437604

Positions:

• chrX-9748675-C-G
• chrX-9748675-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000467482.6(GPR143):​c.456-9G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,142,589 control chromosomes in the GnomAD database, including 1 homozygotes. There are 91 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 0.0013 (1 hom., 42 hem., cov: 23)
  • Exomes 𝑓: 0.00016 (0 hom. 49 hem.)
• Consequence: GPR143 ENST00000467482.6 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006943
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.576

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-9748675-C-G is Benign according to our data. Variant chrX-9748675-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 255711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-9748675-C-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00133 (149/112311) while in subpopulation AFR AF= 0.00475 (147/30968). AF 95% confidence interval is 0.00412. There are 1 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 42 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR143	NM_000273.3	c.456-9G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000467482.6	NP_000264.2
GPR143	XM_005274541.4	c.456-9G>C		splice_polypyrimidine_tract_variant, intron_variant			XP_005274598.1
GPR143	XM_024452388.2	c.204-9G>C		splice_polypyrimidine_tract_variant, intron_variant			XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.456-9G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000273.3	ENSP00000417161	P1
GPR143	ENST00000431126.1	c.204-9G>C		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000406138
GPR143	ENST00000447366.5	c.204-9G>C		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000390546
GPR143	ENST00000480178.1	n.64-9G>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 150 AN: 112258 Hom.: 1 Cov.: 23 AF XY: 0.00122 AC XY: 42 AN XY: 34422

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000939

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000366 AC: 64 AN: 175102 Hom.: 0 AF XY: 0.000196 AC XY: 12 AN XY: 61264

Gnomad AFR exome AF: 0.00482

Gnomad AMR exome AF: 0.000150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.000161 AC: 166 AN: 1030278 Hom.: 0 Cov.: 25 AF XY: 0.000161 AC XY: 49 AN XY: 304222

Gnomad4 AFR exome AF: 0.00599

Gnomad4 AMR exome AF: 0.000172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000128

Gnomad4 OTH exome AF: 0.000137

GnomAD4 genome AF: 0.00133 AC: 149 AN: 112311 Hom.: 1 Cov.: 23 AF XY: 0.00122 AC XY: 42 AN XY: 34485

Gnomad4 AFR AF: 0.00475

Gnomad4 AMR AF: 0.0000937

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.010
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

Other links and lift over

dbSNP: rs376437604; hg19: chrX-9716715;