rs778101223

Variant names:

• chrX-102715048-C-G
• rs778101223
• NM_001004051.4:c.179C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-102715048-C-G
• chrX-102715048-C-T

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.179C>G​(p.Ala60Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 113,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A60V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 24)
• Consequence: GPRASP2 NM_001004051.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• 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: 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=0.09015778).

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.179C>G	p.Ala60Gly	missense	Exon 5 of 5	NP_001004051.1	Q96D09
	GPRASP2	NM_001184874.3		c.179C>G	p.Ala60Gly	missense	Exon 5 of 5	NP_001171803.1	Q96D09
	GPRASP2	NM_001184875.3		c.179C>G	p.Ala60Gly	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.179C>G	p.Ala60Gly	missense	Exon 5 of 5	ENSP00000507692.1	Q96D09
	GPRASP2	ENST00000332262.10	TSL:1	c.179C>G	p.Ala60Gly	missense	Exon 4 of 4	ENSP00000339057.3	Q96D09
	ARMCX5-GPRASP2	ENST00000652409.1		c.-756+782C>G		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes AF: 0.0000176 AC: 2 AN: 113330 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000640

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000176 AC: 2 AN: 113330 Hom.: 0 Cov.: 24 AF XY: 0.0000282 AC XY: 1 AN XY: 35486

African (AFR) AF: 0.0000640 AC: 2 AN: 31248

American (AMR) AF: 0.00 AC: 0 AN: 10842

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53415

Other (OTH) AF: 0.00 AC: 0 AN: 1530

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.42
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.069
Sift	Benign	0.046	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.015	B
Vest4		0.044
MutPred		0.15		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.48
MPC		0.14
ClinPred		0.12	T
GERP RS		3.7
Varity_R		0.096
gMVP		0.089
Mutation Taster		=98/2	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: rs778101223; hg19: chrX-101969976;