NM_001004051.4:c.34G>C

Variant names:

• chrX-102714903-G-C
• NM_001004051.4:c.34G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004051.4(GPRASP2):​c.34G>C​(p.Ala12Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPRASP2 NM_001004051.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

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]

ENSG00000271147 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11480051).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP2	NM_001004051.4	MANE Select	c.34G>C	p.Ala12Pro	missense	Exon 5 of 5	NP_001004051.1	Q96D09
	GPRASP2	NM_001184874.3		c.34G>C	p.Ala12Pro	missense	Exon 5 of 5	NP_001171803.1	Q96D09
	GPRASP2	NM_001184875.3		c.34G>C	p.Ala12Pro	missense	Exon 4 of 4	NP_001171804.1	Q96D09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP2	ENST00000483720.7	TSL:2 MANE Select	c.34G>C	p.Ala12Pro	missense	Exon 5 of 5	ENSP00000507692.1	Q96D09
	GPRASP2	ENST00000332262.10	TSL:1	c.34G>C	p.Ala12Pro	missense	Exon 4 of 4	ENSP00000339057.3	Q96D09
	ARMCX5-GPRASP2	ENST00000652409.1		c.-756+637G>C		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097757 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363147

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35163

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19332

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54011

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841940

Other (OTH) AF: 0.00 AC: 0 AN: 46070

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.042	D
Sift4G	Uncertain	0.021	D
Polyphen		0.77	P
Vest4		0.26
MutPred		0.16		Gain of glycosylation at A12 (P = 0.0205)
MVP		0.35
MPC		0.55
ClinPred		0.27	T
GERP RS		1.7
Varity_R		0.18
gMVP		0.16
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chrX-101969831;