NM_001004051.4:c.203C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004051.4(GPRASP2):​c.203C>G​(p.Ala68Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,144 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.56
Variant links:
Genes affected
GPRASP2 (HGNC:25169): (G protein-coupled receptor associated sorting protein 2) The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.06738463).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPRASP2NM_001004051.4 linkc.203C>G p.Ala68Gly missense_variant Exon 5 of 5 ENST00000483720.7 NP_001004051.1 Q96D09B3KW05

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPRASP2ENST00000483720.7 linkc.203C>G p.Ala68Gly missense_variant Exon 5 of 5 2 NM_001004051.4 ENSP00000507692.1 Q96D09
ARMCX5-GPRASP2ENST00000652409.1 linkc.-756+806C>G intron_variant Intron 4 of 7 ENSP00000498643.1

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1098144
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363550
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
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:
0.00
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Cov.:
25
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.203C>G (p.A68G) alteration is located in exon 5 (coding exon 1) of the GPRASP2 gene. This alteration results from a C to G substitution at nucleotide position 203, causing the alanine (A) at amino acid position 68 to be replaced by a glycine (G). 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
0.080
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.96
CADD
Benign
4.6
DANN
Benign
0.95
DEOGEN2
Benign
0.0050
T;T;T
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.61
.;T;.
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.067
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
L;L;L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.86
N;N;N
REVEL
Benign
0.028
Sift
Benign
0.055
T;T;T
Sift4G
Benign
0.093
T;T;T
Polyphen
0.018
B;B;B
Vest4
0.13
MutPred
0.095
Gain of catalytic residue at A68 (P = 0.0778);Gain of catalytic residue at A68 (P = 0.0778);Gain of catalytic residue at A68 (P = 0.0778);
MVP
0.31
MPC
0.14
ClinPred
0.041
T
GERP RS
2.0
Varity_R
0.068
gMVP
0.048

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.

Other links and lift over

dbSNP: rs779921022; hg19: chrX-101970000; API