17-38462857-C-A

Variant names:

• chr17-38462857-C-A
• rs923947982
• NM_001199417.2:c.265C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001199417.2(ARHGAP23):​c.265C>A​(p.Arg89Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000146 in 1,368,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ARHGAP23 NM_001199417.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22
• Publications: 0 publications found

Genes affected

ARHGAP23 (HGNC:29293): (Rho GTPase activating protein 23) The RHO (see ARHA; MIM 165390) family of small GTPases are involved in signal transduction through transmembrane receptors, and they are inactive in the GDP-bound form and active in the GTP-bound form. GTPase-activating proteins, such as ARHGAP23, inactivate RHO family proteins by stimulating their hydrolysis of GTP (Katoh and Katoh, 2004 [PubMed 15254754]).[supplied by OMIM, Mar 2008]

ENSG00000276170 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199417.2. 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
	ARHGAP23	NM_001199417.2	MANE Select	c.265C>A	p.Arg89Arg	synonymous	Exon 4 of 24	NP_001186346.1	Q9P227-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP23	ENST00000622683.5	TSL:5 MANE Select	c.265C>A	p.Arg89Arg	synonymous	Exon 4 of 24	ENSP00000481862.1	Q9P227-1
	ARHGAP23	ENST00000616767.2	TSL:3	c.607C>A	p.Arg203Arg	synonymous	Exon 4 of 24	ENSP00000516485.1	A0A9L9PXS4
	ARHGAP23	ENST00000633445.2	TSL:3	c.211C>A	p.Arg71Arg	synonymous	Exon 4 of 24	ENSP00000516484.1	A0A9L9PXQ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1368928 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 674024

African (AFR) AF: 0.00 AC: 0 AN: 29506

American (AMR) AF: 0.00 AC: 0 AN: 25824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23862

East Asian (EAS) AF: 0.00 AC: 0 AN: 35394

South Asian (SAS) AF: 0.00 AC: 0 AN: 74504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068548

Other (OTH) AF: 0.00 AC: 0 AN: 56640

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.80
PhyloP100		6.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.80		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.80		Position offset: 2

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

Other links and lift over

dbSNP: rs923947982; hg19: chr17-36619098;