dbSNP rs782780656: ARHGAP4:p.Arg923Pro (chrX-153907802-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001666.5(ARHGAP4):c.2768G>C(p.Arg923Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 896,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000045 ( 0 hom. 1 hem. )

Consequence

ARHGAP4
NM_001666.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.353

Variant links:

Genes affected

ARHGAP4 (HGNC:674): (Rho GTPase activating protein 4) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ARHGAP4 links:

ENSG00000284987 (HGNC:):

ENSG00000284987 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16715571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP4	NM_001666.5 link	c.2768G>C	p.Arg923Pro	missense_variant	Exon 22 of 22	ENST00000350060.10	NP_001657.3	P98171-1
ARHGAP4	NM_001164741.2 link	c.2888G>C	p.Arg963Pro	missense_variant	Exon 23 of 23		NP_001158213.1	P98171-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP4	ENST00000350060.10 link	c.2768G>C	p.Arg923Pro	missense_variant	Exon 22 of 22	1	NM_001666.5	ENSP00000203786.8		P98171-1
ENSG00000284987	ENST00000646191.1 link	n.96+1268G>C		intron_variant	Intron 1 of 4			ENSP00000493873.1		A0A2R8Y4P6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

83783

Hom.:

AF XY:

0.0000337

AC XY:

AN XY:

29661

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000232

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000446

AC:

AN:

896290

Hom.:

Cov.:

AF XY:

0.00000357

AC XY:

AN XY:

280092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000408

Gnomad4 OTH exome

AF:

0.0000276

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000178

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

.;.;T;T

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.90

.;.;P;.

Vest4

0.33

MutPred

0.28

.;.;Loss of MoRF binding (P = 0.002);.;

MVP

0.28

MPC

0.096

ClinPred

0.31

GERP RS

1.9

Varity_R

0.40

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over