X-102654236-CAGAG-C

Position:

• chrX-102654236-CAGAG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001184727.2(GPRASP1):​c.327_330delGAGA​(p.Arg110fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPRASP1 NM_001184727.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.565

Genes affected

GPRASP1 (HGNC:24834): (G protein-coupled receptor associated sorting protein 1) This gene encodes a member of the GPRASP (G protein-coupled receptor associated sorting protein) family. The protein may modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. It targets receptors for degradation in lysosomes. The receptors interacting with this sorting protein include D2 dopamine receptor (DRD2), delta opioid receptor (OPRD1), beta-2 adrenergic receptor (ADRB2), D4 dopamine receptor (DRD4) and cannabinoid 1 receptor (CB1R). Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, May 2010]

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ARMCX5-GPRASP2 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.922 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPRASP1	NM_001184727.2	c.327_330delGAGA	p.Arg110fs	frameshift_variant	6/6	ENST00000537097.2	NP_001171656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPRASP1	ENST00000537097.2	c.327_330delGAGA	p.Arg110fs	frameshift_variant	6/6	2	NM_001184727.2	ENSP00000445683.1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Jan 23, 2024

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101909164;