NM_001142524.2:c.814C>G

Variant names:

• chrX-102749809-C-G
• rs2082527438
• NM_001142524.2:c.814C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142524.2(GPRASP3):​c.814C>G​(p.Arg272Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: GPRASP3 NM_001142524.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.60
• Publications: 0 publications found

Genes affected

GPRASP3 (HGNC:29353): (G protein-coupled receptor associated sorting protein family member 3) This gene is a member of a gene family which encodes proteins with a basic helix-loop-helix domain. Other members of this gene family encode proteins which function as transcription factors, either enhancing or inhibiting transcription depending on the activity of other DNA binding proteins. The coding region of this gene is located entirely within the terminal exon. The encoded protein may be involved in the survival of neurons (PMID: 15034937). Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

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]

LINC00630 (HGNC:44263): (long intergenic non-protein coding RNA 630)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04121381).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142524.2. 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
	GPRASP3	NM_001142524.2	MANE Select	c.814C>G	p.Arg272Gly	missense	Exon 4 of 4	NP_001135996.1	Q6PI77
	GPRASP3	NM_001142525.2		c.814C>G	p.Arg272Gly	missense	Exon 4 of 4	NP_001135997.1	Q6PI77
	GPRASP3	NM_001142526.2		c.814C>G	p.Arg272Gly	missense	Exon 4 of 4	NP_001135998.1	Q6PI77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP3	ENST00000457056.6	TSL:4 MANE Select	c.814C>G	p.Arg272Gly	missense	Exon 4 of 4	ENSP00000403226.1	Q6PI77
	GPRASP3	ENST00000361229.8	TSL:1	c.814C>G	p.Arg272Gly	missense	Exon 3 of 3	ENSP00000354675.4	Q6PI77
	ARMCX5-GPRASP2	ENST00000652409.1		c.814C>G	p.Arg272Gly	missense	Exon 8 of 8	ENSP00000498643.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 362628

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

American (AMR) AF: 0.00 AC: 0 AN: 35086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19270

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 53933

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841638

Other (OTH) AF: 0.00 AC: 0 AN: 46047

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000936 Hom.: 0

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	0.075
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0080
DANN	Benign	0.64
DEOGEN2	Benign	0.0036	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		-2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.017
Sift	Benign	0.47	T
Sift4G	Benign	0.53	T
Polyphen		0.051	B
Vest4		0.12
MutPred		0.20		Loss of loop (P = 0.0112)
MVP		0.048
MPC		0.12
ClinPred		0.054	T
GERP RS		-3.6
Varity_R		0.050
gMVP		0.28
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: rs2082527438; hg19: chrX-102004737;