Genetic Variant NM_001004051.4:c.441G>C (chrX-102715310-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004051.4(GPRASP2):c.441G>C(p.Gln147His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 25)

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130

Publications

0 publications found

Variant links:

Genes affected

GPRASP2 (HGNC:25169): (G protein-coupled receptor associated sorting protein 2) The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

GPRASP2 links:

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]

ARMCX5-GPRASP2 links:

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ACMG classification

Classification was made for transcript

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=0.07930344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	NM_001004051.4	MANE Select	c.441G>C	p.Gln147His	missense	Exon 5 of 5	NP_001004051.1	Q96D09
GPRASP2	NM_001184874.3		c.441G>C	p.Gln147His	missense	Exon 5 of 5	NP_001171803.1	Q96D09
GPRASP2	NM_001184875.3		c.441G>C	p.Gln147His	missense	Exon 4 of 4	NP_001171804.1	Q96D09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	ENST00000483720.7	TSL:2 MANE Select	c.441G>C	p.Gln147His	missense	Exon 5 of 5	ENSP00000507692.1	Q96D09
GPRASP2	ENST00000332262.10	TSL:1	c.441G>C	p.Gln147His	missense	Exon 4 of 4	ENSP00000339057.3	Q96D09
ARMCX5-GPRASP2	ENST00000652409.1		c.-756+1044G>C		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.92

CADD

Benign

9.3

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.075

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.65

M_CAP

Benign

0.0069

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.13

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.9

REVEL

Benign

0.010

Sift

Uncertain

0.023

Sift4G

Uncertain

0.014

Polyphen

0.0010

Vest4

0.016

MutPred

0.26

Loss of disorder (P = 0.0679)

MVP

0.29

MPC

0.13

ClinPred

0.15

GERP RS

-4.3

Varity_R

0.10

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over