rs1175455167

Positions:

• chrX-9765656-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000273.3(GPR143):​c.162C>T​(p.Pro54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 874,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000030 (0 hom. 9 hem.)
• Consequence: GPR143 NM_000273.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-9765656-G-A is Benign according to our data. Variant chrX-9765656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.379 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR143	NM_000273.3	c.162C>T	p.Pro54=	synonymous_variant	1/9	ENST00000467482.6
GPR143	XM_005274541.4	c.162C>T	p.Pro54=	synonymous_variant	1/9
GPR143	XM_024452388.2	c.-2-4830C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR143	ENST00000467482.6	c.162C>T	p.Pro54=	synonymous_variant	1/9	1	NM_000273.3	P1
GPR143	ENST00000431126.1	c.-3+464C>T		intron_variant		3
GPR143	ENST00000447366.5	c.-2-4830C>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.0000297 AC: 26 AN: 874297 Hom.: 0 Cov.: 27 AF XY: 0.0000331 AC XY: 9 AN XY: 271625

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000340

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 09, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs1175455167; hg19: chrX-9733696;