rs1175455167

Variant names:

• chrX-9765656-G-A
• rs1175455167
• NM_000273.3:c.162C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000273.3(GPR143):​c.162C>T​(p.Pro54Pro) 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
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GPR143	NM_000273.3	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 9	ENST00000467482.6	NP_000264.2
GPR143	NM_001440781.1	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 9		NP_001427710.1
GPR143	XM_024452388.2	c.-2-4830C>T		intron_variant	Intron 1 of 8		XP_024308156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR143	ENST00000467482.6	c.162C>T	p.Pro54Pro	synonymous_variant	Exon 1 of 9	1	NM_000273.3	ENSP00000417161.1
GPR143	ENST00000447366.5	c.-2-4830C>T		intron_variant	Intron 1 of 7	3		ENSP00000390546.2
GPR143	ENST00000431126.1	c.-3+464C>T		intron_variant	Intron 1 of 5	3		ENSP00000406138.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00 AC: 0 AN: 4210 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 18171

American (AMR) AF: 0.000142 AC: 1 AN: 7043

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11433

East Asian (EAS) AF: 0.00 AC: 0 AN: 20074

South Asian (SAS) AF: 0.00 AC: 0 AN: 23981

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2202

European-Non Finnish (NFE) AF: 0.0000340 AC: 25 AN: 735125

Other (OTH) AF: 0.00 AC: 0 AN: 36071

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 09, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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
PhyloP100		0.38
PromoterAI		0.021	Neutral

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

Other links and lift over

dbSNP: rs1175455167; hg19: chrX-9733696;