22-44802085-CGC-TGT

Variant names:

• chr22-44802085-CGC-TGT
• NM_181335.3:c.88_90delCGCinsTGT
• ARHGAP8 p.Arg30Cys

Variant summary

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

The NM_181335.3(ARHGAP8):​c.88_90delCGCinsTGT​(p.Arg30Cys) 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. R30G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP8 NM_181335.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 0 publications found

Genes affected

ARHGAP8 (HGNC:677): (Rho GTPase activating protein 8) This gene encodes a member of the RHOGAP family. GAP (GTPase-activating) family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. GAP proteins alternate between an active (GTP-bound) and inactive (GDP-bound) state based on the GTP:GDP ratio in the cell. This family member is a multidomain protein that functions to promote Erk activation and cell motility. Alternative splicing results in multiple transcript variants. Read-through transcripts from the upstream proline rich 5, renal (PRR5) gene into this gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

PRR5-ARHGAP8 (HGNC:34512): (PRR5-ARHGAP8 readthrough) The PRR5-ARHGAP8 mRNA is an infrequent but naturally occurring read-through transcript of the neighboring proline rich 5, renal (PRR5) and Rho GTPase activating protein 8 (ARHGAP8) genes. The resulting fusion protein contains sequence identity with each individual gene product, and it includes domains characteristic of a RhoGAP protein. The significance of this read-through transcript and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2010]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181335.3. 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
	ARHGAP8	NM_181335.3	MANE Select	c.88_90delCGCinsTGT	p.Arg30Cys	missense	N/A	NP_851852.2	P85298-4
	PRR5-ARHGAP8	NM_181334.6		c.481_483delCGCinsTGT	p.Arg161Cys	missense	N/A	NP_851851.3	B1AHC3
	ARHGAP8	NM_001017526.2		c.88_90delCGCinsTGT	p.Arg30Cys	missense	N/A	NP_001017526.1	P85298-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP8	ENST00000356099.11	TSL:1 MANE Select	c.88_90delCGCinsTGT	p.Arg30Cys	missense	N/A	ENSP00000348407.6	P85298-4
	PRR5-ARHGAP8	ENST00000352766.11	TSL:2	c.850_852delCGCinsTGT	p.Arg284Cys	missense	N/A	ENSP00000262731.11	B1AHC4
	ARHGAP8	ENST00000336963.8	TSL:1	c.88_90delCGCinsTGT	p.Arg30Cys	missense	N/A	ENSP00000337287.4	P85298-5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

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: chr22-45197965;