X-102715156-C-T

Variant names:

• chrX-102715156-C-T
• rs759762709
• NM_001004051.4:c.287C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001004051.4(GPRASP2):​c.287C>T​(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,211,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000019 (0 hom. 8 hem.)
• Consequence: GPRASP2 NM_001004051.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.364
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15499327).
• BS2: High Hemizygotes in GnomAdExome4 at 8 Unknown,XL gene

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.287C>T	p.Ala96Val	missense	Exon 5 of 5	NP_001004051.1	Q96D09
	GPRASP2	NM_001184874.3		c.287C>T	p.Ala96Val	missense	Exon 5 of 5	NP_001171803.1	Q96D09
	GPRASP2	NM_001184875.3		c.287C>T	p.Ala96Val	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.287C>T	p.Ala96Val	missense	Exon 5 of 5	ENSP00000507692.1	Q96D09
	GPRASP2	ENST00000332262.10	TSL:1	c.287C>T	p.Ala96Val	missense	Exon 4 of 4	ENSP00000339057.3	Q96D09
	ARMCX5-GPRASP2	ENST00000652409.1		c.-756+890C>T		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 3 AN: 113437 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000561

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182694 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000191 AC: 21 AN: 1098163 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 8 AN XY: 363543

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40487

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000249 AC: 21 AN: 842103

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome AF: 0.0000264 AC: 3 AN: 113437 Hom.: 0 Cov.: 24 AF XY: 0.0000281 AC XY: 1 AN XY: 35583

African (AFR) AF: 0.00 AC: 0 AN: 31285

American (AMR) AF: 0.00 AC: 0 AN: 10849

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.00 AC: 0 AN: 2808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000561 AC: 3 AN: 53442

Other (OTH) AF: 0.00 AC: 0 AN: 1532

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.36
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.15
Sift	Uncertain	0.018	D
Sift4G	Benign	0.10	T
Polyphen		0.80	P
Vest4		0.12
MutPred		0.15		Loss of methylation at R97 (P = 0.0946)
MVP		0.35
MPC		0.62
ClinPred		0.52	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.19
Mutation Taster		=100/0	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

dbSNP: rs759762709; hg19: chrX-101970084;