rs2070097

chrX-153910800-A-CchrX-153910800-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001666.5(ARHGAP4):c.1716T>G(p.His572Gln) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H572H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ARHGAP4 NM_001666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

ACMG classification

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=0.17348105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP4	NM_001666.5	c.1716T>G	p.His572Gln	missense_variant	15/22	ENST00000350060.10
ARHGAP4	NM_001164741.2	c.1836T>G	p.His612Gln	missense_variant	16/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP4	ENST00000350060.10	c.1716T>G	p.His572Gln	missense_variant	15/22	1	NM_001666.5	P2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.0040
Dann	Benign	0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Benign	0.036
Sift	Benign	0.044	D;D;D;D
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.031	.;.;B;.
Vest4		0.14
MutPred		0.52		.;.;Loss of catalytic residue at D573 (P = 0.063);.;
MVP		0.25
MPC		0.027
ClinPred		0.090	T
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2070097; hg19: chrX-153176254;