X-153907801-CC-AG

Variant names:

• chrX-153907801-CC-AG
• NM_001666.5:c.2768_2769delGGinsCT
• ARHGAP4 p.Arg923Pro

Variant summary

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

The NM_001666.5(ARHGAP4):​c.2768_2769delGGinsCT​(p.Arg923Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R923Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: ARHGAP4 NM_001666.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000284987 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP4	NM_001666.5	MANE Select	c.2768_2769delGGinsCT	p.Arg923Pro	missense	N/A	NP_001657.3
	ARHGAP4	NM_001164741.2		c.2888_2889delGGinsCT	p.Arg963Pro	missense	N/A	NP_001158213.1	P98171-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP4	ENST00000350060.10	TSL:1 MANE Select	c.2768_2769delGGinsCT	p.Arg923Pro	missense	N/A	ENSP00000203786.8	P98171-1
	ARHGAP4	ENST00000370028.7	TSL:1	c.2888_2889delGGinsCT	p.Arg963Pro	missense	N/A	ENSP00000359045.3	P98171-2
	ENSG00000284987	ENST00000646191.1		n.96+1268_96+1269delGGinsCT		intron	N/A	ENSP00000493873.1	A0A2R8Y4P6

Frequencies

GnomAD3 genomes Cov.: 25

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-153173255;