Variant X-102655271-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001184727.2(GPRASP1):c.1358G>C(p.Ser453Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,141 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

GPRASP1
NM_001184727.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.61

Variant links:

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]

GPRASP1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06876847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP1	NM_001184727.2 linkuse as main transcript	c.1358G>C	p.Ser453Thr	missense_variant	6/6	ENST00000537097.2
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.649+49618G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRASP1	ENST00000537097.2 linkuse as main transcript	c.1358G>C	p.Ser453Thr	missense_variant	6/6	2	NM_001184727.2	P1
	ENST00000602441.1 linkuse as main transcript	n.57+4385C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183447

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67889

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098141

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363495

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.1358G>C (p.S453T) alteration is located in exon 6 (coding exon 1) of the GPRASP1 gene. This alteration results from a G to C substitution at nucleotide position 1358, causing the serine (S) at amino acid position 453 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0050

DANN

Benign

0.54

DEOGEN2

Benign

0.051

T;T;T;T

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.30

.;.;.;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.66

N;N;N;N

REVEL

Benign

0.038

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.59

P;P;P;P

Vest4

0.14

MutPred

0.15

Gain of glycosylation at S452 (P = 0.051);Gain of glycosylation at S452 (P = 0.051);Gain of glycosylation at S452 (P = 0.051);Gain of glycosylation at S452 (P = 0.051);

MVP

0.43

MPC

0.20

ClinPred

0.068

GERP RS

-3.8

Varity_R

0.075

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over