rs777310873

Variant names:

• chr17-38428541-C-T
• rs777310873
• NM_001199417.2:c.56C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001199417.2(ARHGAP23):​c.56C>T​(p.Pro19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,451,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (1 hom.)
• Consequence: ARHGAP23 NM_001199417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11461705).

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.56C>T	p.Pro19Leu	missense	Exon 1 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.56C>T	p.Pro19Leu	missense	Exon 1 of 24	ENSP00000481862.1	Q9P227-1
	ARHGAP23	ENST00000620417.4	TSL:5	c.56C>T	p.Pro19Leu	missense	Exon 1 of 25	ENSP00000482992.1	Q9P227-2
	ARHGAP23	ENST00000633445.2	TSL:3	c.9+9142C>T		intron	N/A	ENSP00000516484.1	A0A9L9PXQ2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000934 AC: 7 AN: 74954 AF XY: 0.0000926

Gnomad AFR exome AF: 0.00

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: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000392 AC: 51 AN: 1299612 Hom.: 1 Cov.: 30 AF XY: 0.0000469 AC XY: 30 AN XY: 640282

African (AFR) AF: 0.00 AC: 0 AN: 26608

American (AMR) AF: 0.00 AC: 0 AN: 25590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22894

East Asian (EAS) AF: 0.00 AC: 0 AN: 27728

South Asian (SAS) AF: 0.000229 AC: 16 AN: 69986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3854

European-Non Finnish (NFE) AF: 0.0000337 AC: 35 AN: 1037088

Other (OTH) AF: 0.00 AC: 0 AN: 53592

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.000150 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.27	N
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.54	T
Vest4		0.18
MVP		0.47
ClinPred		0.30	T
GERP RS		2.9
PromoterAI		0.017	Neutral
Varity_R		0.11
gMVP		0.45
Mutation Taster		=100/0	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: rs777310873; hg19: chr17-36584785;