X-102654696-C-G

Variant names:

• chrX-102654696-C-G
• rs145935226
• NM_001184727.2:c.783C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001184727.2(GPRASP1):​c.783C>G​(p.Pro261Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,209,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00017 (0 hom. 64 hem.)
• Consequence: GPRASP1 NM_001184727.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-102654696-C-G is Benign according to our data. Variant chrX-102654696-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2661079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.046 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 5 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.783C>G	p.Pro261Pro	synonymous	Exon 6 of 6	NP_001171656.1	Q5JY77
	GPRASP1	NM_001099410.2		c.783C>G	p.Pro261Pro	synonymous	Exon 4 of 4	NP_001092880.1	Q5JY77
	GPRASP1	NM_001099411.2		c.783C>G	p.Pro261Pro	synonymous	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.783C>G	p.Pro261Pro	synonymous	Exon 6 of 6	ENSP00000445683.1	Q5JY77
	GPRASP1	ENST00000361600.9	TSL:2	c.783C>G	p.Pro261Pro	synonymous	Exon 5 of 5	ENSP00000355146.4	Q5JY77
	GPRASP1	ENST00000415986.5	TSL:4	c.783C>G	p.Pro261Pro	synonymous	Exon 4 of 4	ENSP00000393691.1	Q5JY77

Frequencies

GnomAD3 genomes AF: 0.000187 AC: 21 AN: 112122 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

Gnomad ASJ AF: 0.00114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000263

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000196 AC: 36 AN: 183289 AF XY: 0.000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.00107

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000232

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000166 AC: 182 AN: 1097747 Hom.: 0 Cov.: 30 AF XY: 0.000176 AC XY: 64 AN XY: 363101

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.000227 AC: 8 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00150 AC: 29 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54135

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.000484 AC: 2 AN: 4132

European-Non Finnish (NFE) AF: 0.000162 AC: 136 AN: 841701

Other (OTH) AF: 0.000152 AC: 7 AN: 46077

GnomAD4 genome AF: 0.000187 AC: 21 AN: 112178 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34368

African (AFR) AF: 0.00 AC: 0 AN: 30902

American (AMR) AF: 0.000376 AC: 4 AN: 10649

Ashkenazi Jewish (ASJ) AF: 0.00114 AC: 3 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000263 AC: 14 AN: 53220

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.000521 Hom.: 3

Bravo AF: 0.000193

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.046
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: rs145935226; hg19: chrX-101909624;