X-102749943-G-A

Variant names:

• chrX-102749943-G-A
• rs781012955
• NM_001142524.2:c.948G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142524.2(GPRASP3):​c.948G>A​(p.Met316Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: GPRASP3 NM_001142524.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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: 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=0.20732352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRASP3	NM_001142524.2	c.948G>A	p.Met316Ile	missense_variant	Exon 4 of 4	ENST00000457056.6	NP_001135996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRASP3	ENST00000457056.6	c.948G>A	p.Met316Ile	missense_variant	Exon 4 of 4	4	NM_001142524.2	ENSP00000403226.1
ARMCX5-GPRASP2	ENST00000652409.1	c.948G>A	p.Met316Ile	missense_variant	Exon 8 of 8			ENSP00000498643.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T;T;T;T;T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.59	.;.;.;T;.
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;M;M;M;M
PhyloP100		3.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.51	T;T;T;T;T
Sift4G	Uncertain	0.039	D;D;D;D;D
Polyphen		0.63	P;P;P;P;P
Vest4		0.35
MutPred		0.39		Gain of ubiquitination at K315 (P = 0.1245);Gain of ubiquitination at K315 (P = 0.1245);Gain of ubiquitination at K315 (P = 0.1245);Gain of ubiquitination at K315 (P = 0.1245);Gain of ubiquitination at K315 (P = 0.1245);
MVP		0.54
MPC		0.11
ClinPred		0.63	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.21
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

Publications

Loading publications...

Other links and lift over

dbSNP: rs781012955; hg19: chrX-102004871;