rs11095520

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-9760704-G-C
• chrX-9760704-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000273.3(GPR143):​c.360+13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 975,278 control chromosomes in the GnomAD database, including 2,722 homozygotes. There are 22,440 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (382 hom., 2592 hem., cov: 22)
  • Exomes 𝑓: 0.082 (2340 hom. 19848 hem.)
• Consequence: GPR143 NM_000273.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O: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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-9760704-G-C is Benign according to our data. Variant chrX-9760704-G-C is described in ClinVar as Benign. ClinVar VariationId is 98629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

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>G		intron	N/A	NP_000264.2
	GPR143	NM_001440781.1		c.360+13C>G		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>G		intron	N/A	ENSP00000417161.1
	GPR143	ENST00000929114.1		c.360+13C>G		intron	N/A	ENSP00000599173.1
	GPR143	ENST00000929113.1		c.360+13C>G		intron	N/A	ENSP00000599172.1

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 9778 AN: 110653 Hom.: 383 Cov.: 22

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0162

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0322

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.0979

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0740 AC: 11500 AN: 155426 AF XY: 0.0695

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0447

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.0366

Gnomad FIN exome AF: 0.0757

Gnomad NFE exome AF: 0.0866

Gnomad OTH exome AF: 0.0869

GnomAD4 exome AF: 0.0823 AC: 71122 AN: 864572 Hom.: 2340 Cov.: 15 AF XY: 0.0810 AC XY: 19848 AN XY: 245168

African (AFR) AF: 0.118 AC: 2612 AN: 22149

American (AMR) AF: 0.0502 AC: 1656 AN: 32988

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 2347 AN: 17645

East Asian (EAS) AF: 0.0333 AC: 962 AN: 28911

South Asian (SAS) AF: 0.0298 AC: 1407 AN: 47202

European-Finnish (FIN) AF: 0.0763 AC: 3015 AN: 39526

Middle Eastern (MID) AF: 0.0815 AC: 283 AN: 3473

European-Non Finnish (NFE) AF: 0.0876 AC: 55566 AN: 634325

Other (OTH) AF: 0.0854 AC: 3274 AN: 38353

GnomAD4 genome AF: 0.0883 AC: 9771 AN: 110706 Hom.: 382 Cov.: 22 AF XY: 0.0786 AC XY: 2592 AN XY: 32958

African (AFR) AF: 0.113 AC: 3429 AN: 30423

American (AMR) AF: 0.0635 AC: 652 AN: 10263

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 349 AN: 2634

East Asian (EAS) AF: 0.0399 AC: 142 AN: 3561

South Asian (SAS) AF: 0.0319 AC: 83 AN: 2601

European-Finnish (FIN) AF: 0.0685 AC: 405 AN: 5912

Middle Eastern (MID) AF: 0.0935 AC: 20 AN: 214

European-Non Finnish (NFE) AF: 0.0856 AC: 4532 AN: 52916

Other (OTH) AF: 0.0985 AC: 148 AN: 1502

Alfa AF: 0.0564 Hom.: 423

Bravo AF: 0.0921

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.33
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV66633438; COSMIC: COSV66633438;