X-102715045-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004051.4(GPRASP2):​c.176C>T​(p.Ala59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,211,156 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes 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: 𝑓 0.000044 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000051 ( 0 hom. 25 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.02909705).
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPRASP2NM_001004051.4 linkuse as main transcriptc.176C>T p.Ala59Val missense_variant 5/5 ENST00000483720.7
ARMCX5-GPRASP2NR_146584.3 linkuse as main transcriptn.795+779C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPRASP2ENST00000483720.7 linkuse as main transcriptc.176C>T p.Ala59Val missense_variant 5/52 NM_001004051.4 P1
ARMCX5-GPRASP2ENST00000652409.1 linkuse as main transcriptc.-756+779C>T intron_variant P1

Frequencies

GnomAD3 genomes
AF:
0.0000443
AC:
5
AN:
112950
Hom.:
0
Cov.:
24
AF XY:
0.0000568
AC XY:
2
AN XY:
35188
show subpopulations
Gnomad AFR
AF:
0.0000642
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000280
Gnomad SAS
AF:
0.000361
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000982
AC:
18
AN:
183362
Hom.:
0
AF XY:
0.000103
AC XY:
7
AN XY:
67824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000649
Gnomad SAS exome
AF:
0.000367
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000510
AC:
56
AN:
1098206
Hom.:
0
Cov.:
31
AF XY:
0.0000688
AC XY:
25
AN XY:
363574
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000364
Gnomad4 SAS exome
AF:
0.000443
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000178
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000443
AC:
5
AN:
112950
Hom.:
0
Cov.:
24
AF XY:
0.0000568
AC XY:
2
AN XY:
35188
show subpopulations
Gnomad4 AFR
AF:
0.0000642
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000280
Gnomad4 SAS
AF:
0.000361
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsMay 13, 2024The c.176C>T (p.A59V) alteration is located in exon 5 (coding exon 1) of the GPRASP2 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the alanine (A) at amino acid position 59 to be replaced by a valine (V). 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
0.089
BayesDel_addAF
Benign
-0.84
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
10
DANN
Benign
0.82
DEOGEN2
Benign
0.0032
T;T;T
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.43
.;T;.
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.029
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.34
N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.60
N;N;N
REVEL
Benign
0.060
Sift
Benign
0.093
T;T;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.018
MutPred
0.11
Gain of methylation at K63 (P = 0.0845);Gain of methylation at K63 (P = 0.0845);Gain of methylation at K63 (P = 0.0845);
MVP
0.30
MPC
0.14
ClinPred
0.012
T
GERP RS
1.8
Varity_R
0.035
gMVP
0.066

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: rs1327200158; hg19: chrX-101969973; API