rs923947982

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-38462857-C-T
• chr17-38462857-C-A
• chr17-38462857-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001199417.2(ARHGAP23):​c.265C>T​(p.Arg89Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,521,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ARHGAP23 NM_001199417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37297454).

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>T	p.Arg89Trp	missense	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>T	p.Arg89Trp	missense	Exon 4 of 24	ENSP00000481862.1	Q9P227-1
	ARHGAP23	ENST00000618942.1	TSL:5	c.-18C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 7	ENSP00000482982.1	A0A087WZZ2
	ARHGAP23	ENST00000616767.2	TSL:3	c.607C>T	p.Arg203Trp	missense	Exon 4 of 24	ENSP00000516485.1	A0A9L9PXS4

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000233 AC: 3 AN: 128724 AF XY: 0.00

Gnomad AFR exome AF: 0.000270

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000189

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000300 AC: 41 AN: 1368924 Hom.: 0 Cov.: 31 AF XY: 0.0000297 AC XY: 20 AN XY: 674020

African (AFR) AF: 0.000508 AC: 15 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: 0.0000565 AC: 2 AN: 35392

South Asian (SAS) AF: 0.000121 AC: 9 AN: 74504

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

Middle Eastern (MID) AF: 0.000536 AC: 3 AN: 5596

European-Non Finnish (NFE) AF: 0.00000562 AC: 6 AN: 1068546

Other (OTH) AF: 0.000106 AC: 6 AN: 56640

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74474

African (AFR) AF: 0.000168 AC: 7 AN: 41568

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.2
PrimateAI	Uncertain	0.71	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.57
MVP		0.56
ClinPred		0.83	D
GERP RS		5.2
Varity_R		0.25
gMVP		0.60
Mutation Taster		=288/12	polymorphism

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

Other links and lift over

dbSNP: rs923947982; hg19: chr17-36619098;