NM_001184727.2:c.11C>A

Variant names:

• chrX-102653924-C-A
• rs761365941
• NM_001184727.2:c.11C>A

Variant summary

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

The NM_001184727.2(GPRASP1):​c.11C>A​(p.Ala4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,205,773 control chromosomes in the GnomAD database, including 1 homozygotes. There are 4 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 0.000098 (1 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.0000037 (0 hom. 0 hem.)
• Consequence: GPRASP1 NM_001184727.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

GPRASP1 (HGNC:24834): (G protein-coupled receptor associated sorting protein 1) This gene encodes a member of the GPRASP (G protein-coupled receptor associated sorting protein) family. The protein may modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. It targets receptors for degradation in lysosomes. The receptors interacting with this sorting protein include D2 dopamine receptor (DRD2), delta opioid receptor (OPRD1), beta-2 adrenergic receptor (ADRB2), D4 dopamine receptor (DRD4) and cannabinoid 1 receptor (CB1R). Multiple alternatively spliced transcript variants encoding the same protein have been identified. [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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08948088).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184727.2. 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
	GPRASP1	NM_001184727.2	MANE Select	c.11C>A	p.Ala4Glu	missense	Exon 6 of 6	NP_001171656.1	Q5JY77
	GPRASP1	NM_001099410.2		c.11C>A	p.Ala4Glu	missense	Exon 4 of 4	NP_001092880.1	Q5JY77
	GPRASP1	NM_001099411.2		c.11C>A	p.Ala4Glu	missense	Exon 3 of 3	NP_001092881.1	Q5JY77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP1	ENST00000537097.2	TSL:2 MANE Select	c.11C>A	p.Ala4Glu	missense	Exon 6 of 6	ENSP00000445683.1	Q5JY77
	GPRASP1	ENST00000361600.9	TSL:2	c.11C>A	p.Ala4Glu	missense	Exon 5 of 5	ENSP00000355146.4	Q5JY77
	GPRASP1	ENST00000415986.5	TSL:4	c.11C>A	p.Ala4Glu	missense	Exon 4 of 4	ENSP00000393691.1	Q5JY77

Frequencies

GnomAD3 genomes AF: 0.0000980 AC: 11 AN: 112276 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000842

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: 0.000663

GnomAD2 exomes AF: 0.00000557 AC: 1 AN: 179665 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000371

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000366 AC: 4 AN: 1093442 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 359216

African (AFR) AF: 0.0000380 AC: 1 AN: 26295

American (AMR) AF: 0.0000286 AC: 1 AN: 34965

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19191

East Asian (EAS) AF: 0.00 AC: 0 AN: 30166

South Asian (SAS) AF: 0.00 AC: 0 AN: 53784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4109

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 838553

Other (OTH) AF: 0.0000436 AC: 2 AN: 45905

GnomAD4 genome AF: 0.0000979 AC: 11 AN: 112331 Hom.: 1 Cov.: 24 AF XY: 0.000116 AC XY: 4 AN XY: 34499

African (AFR) AF: 0.0000324 AC: 1 AN: 30904

American (AMR) AF: 0.000841 AC: 9 AN: 10702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00 AC: 0 AN: 2705

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6133

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53239

Other (OTH) AF: 0.000655 AC: 1 AN: 1527

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000219

ExAC AF: 0.0000165 AC: 2

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	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.77
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.27
MutPred		0.092		Loss of glycosylation at T2 (P = 0.0961)
MVP		0.24
MPC		0.57
ClinPred		0.51	D
GERP RS		2.2
Varity_R		0.36
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: rs761365941; hg19: chrX-101908852;