X-102653934-G-A

Variant names:

• chrX-102653934-G-A
• rs147883400
• NM_001184727.2:c.21G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001184727.2(GPRASP1):​c.21G>A​(p.Glu7Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,529 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: GPRASP1 NM_001184727.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.923 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.21G>A	p.Glu7Glu	synonymous	Exon 6 of 6	NP_001171656.1	Q5JY77
	GPRASP1	NM_001099410.2		c.21G>A	p.Glu7Glu	synonymous	Exon 4 of 4	NP_001092880.1	Q5JY77
	GPRASP1	NM_001099411.2		c.21G>A	p.Glu7Glu	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.21G>A	p.Glu7Glu	synonymous	Exon 6 of 6	ENSP00000445683.1	Q5JY77
	GPRASP1	ENST00000361600.9	TSL:2	c.21G>A	p.Glu7Glu	synonymous	Exon 5 of 5	ENSP00000355146.4	Q5JY77
	GPRASP1	ENST00000415986.5	TSL:4	c.21G>A	p.Glu7Glu	synonymous	Exon 4 of 4	ENSP00000393691.1	Q5JY77

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112503 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000970

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

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181433 AF XY: 0.00

Gnomad AFR exome AF: 0.0000763

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096026 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 2 AN XY: 361498

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.00 AC: 0 AN: 35105

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19306

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 53985

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40511

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840448

Other (OTH) AF: 0.00 AC: 0 AN: 46011

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112503 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34653

African (AFR) AF: 0.0000970 AC: 3 AN: 30921

American (AMR) AF: 0.00 AC: 0 AN: 10698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 2730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53308

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.36
PhyloP100		0.92

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: rs147883400; hg19: chrX-101908862;