rs139058246

Variant names:

• chrX-153907892-C-A
• NM_001666.5:c.2678G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153907892-C-A
• chrX-153907892-C-T

Variant summary

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

The NM_001666.5(ARHGAP4):​c.2678G>T​(p.Gly893Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000106 in 945,421 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. 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.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000011 (0 hom. 0 hem.)
• Consequence: ARHGAP4 NM_001666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981

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]

ENSG00000284987 (HGNC:):

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=0.1375725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP4	NM_001666.5	c.2678G>T	p.Gly893Val	missense_variant	Exon 22 of 22	ENST00000350060.10	NP_001657.3
ARHGAP4	NM_001164741.2	c.2798G>T	p.Gly933Val	missense_variant	Exon 23 of 23		NP_001158213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP4	ENST00000350060.10	c.2678G>T	p.Gly893Val	missense_variant	Exon 22 of 22	1	NM_001666.5	ENSP00000203786.8
ENSG00000284987	ENST00000646191.1	n.96+1178G>T		intron_variant	Intron 1 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000106 AC: 1 AN: 945421 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 294515

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: 0.00000131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.12	.;.;T;T
FATHMM_MKL	Benign	0.040	N
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	.;.;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N;D;D;D
REVEL	Benign	0.096
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.17
MutPred		0.24		.;.;Gain of sheet (P = 0.0477);.;
MVP		0.27
MPC		0.13
ClinPred		0.44	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153173346;