X-9760704-G-T

Variant names:

• chrX-9760704-G-T
• rs11095520
• NM_000273.3:c.360+13C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000273.3(GPR143):​c.360+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 975,844 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 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 0.00014 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.00013 (0 hom. 19 hem.)
• Consequence: GPR143 NM_000273.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.174
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-9760704-G-T is Benign according to our data. Variant chrX-9760704-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1634329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000145 (16/110672) while in subpopulation NFE AF = 0.000302 (16/52931). AF 95% confidence interval is 0.000189. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	NM_000273.3	MANE Select	c.360+13C>A		intron	N/A	NP_000264.2
	GPR143	NM_001440781.1		c.360+13C>A		intron	N/A	NP_001427710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	ENST00000467482.6	TSL:1 MANE Select	c.360+13C>A		intron	N/A	ENSP00000417161.1
	GPR143	ENST00000929114.1		c.360+13C>A		intron	N/A	ENSP00000599173.1
	GPR143	ENST00000929113.1		c.360+13C>A		intron	N/A	ENSP00000599172.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 16 AN: 110672 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000302

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000901 AC: 14 AN: 155426 AF XY: 0.0000835

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: 0.000210

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000126 AC: 109 AN: 865172 Hom.: 0 Cov.: 15 AF XY: 0.0000775 AC XY: 19 AN XY: 245218

African (AFR) AF: 0.00 AC: 0 AN: 22157

American (AMR) AF: 0.00 AC: 0 AN: 32997

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17653

East Asian (EAS) AF: 0.00 AC: 0 AN: 28911

South Asian (SAS) AF: 0.00 AC: 0 AN: 47211

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39537

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3475

European-Non Finnish (NFE) AF: 0.000164 AC: 104 AN: 634861

Other (OTH) AF: 0.000130 AC: 5 AN: 38370

GnomAD4 genome AF: 0.000145 AC: 16 AN: 110672 Hom.: 0 Cov.: 22 AF XY: 0.000122 AC XY: 4 AN XY: 32900

African (AFR) AF: 0.00 AC: 0 AN: 30362

American (AMR) AF: 0.00 AC: 0 AN: 10252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2609

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.000302 AC: 16 AN: 52931

Other (OTH) AF: 0.00 AC: 0 AN: 1485

Alfa AF: 0.0000386 Hom.: 423

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.53
DANN	Benign	0.39
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11095520; hg19: chrX-9728744;