X-102654110-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001184727.2(GPRASP1):c.197T>A(p.Val66Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPRASP1 NM_001184727.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.52

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05010727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP1	NM_001184727.2	c.197T>A	p.Val66Asp	missense_variant	6/6	ENST00000537097.2
ARMCX5-GPRASP2	NR_146584.3	n.649+48457T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRASP1	ENST00000537097.2	c.197T>A	p.Val66Asp	missense_variant	6/6	2	NM_001184727.2	P1
	ENST00000602441.1	n.58-4396A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

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

Illumina Laboratory Services, Illumina

Sep 22, 2021

The GPRASP1 c.197T>A (p.Val66Asp) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in version 2.1.1 or version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequencing coverage, which suggest the variant is rare. Multiple lines of computational evidence suggest that this variant will have no impact on the gene or gene product, though these predictions have not been confirmed experimentally. Based on the available evidence, the p.Val66Asp variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.9
Dann	Benign	0.93
DEOGEN2	Benign	0.098	T;T;T;T
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.94	N;N;N;N
REVEL	Benign	0.033
Sift	Uncertain	0.018	D;D;D;D
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.36	B;B;B;B
Vest4		0.20
MutPred		0.21		Loss of MoRF binding (P = 0.0193);Loss of MoRF binding (P = 0.0193);Loss of MoRF binding (P = 0.0193);Loss of MoRF binding (P = 0.0193);
MVP		0.068
MPC		0.24
ClinPred		0.069	T
GERP RS		-1.8
Varity_R		0.14

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-101909038;