Variant 17-38466510-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199417.2(ARHGAP23):c.827G>A(p.Arg276Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000045 in 1,332,540 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: not found (cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

ARHGAP23
NM_001199417.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

Variant links:

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]

ARHGAP23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1225068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP23	NM_001199417.2 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	7/24	ENST00000622683.5	NP_001186346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP23	ENST00000622683.5 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	7/24	5	NM_001199417.2	ENSP00000481862	P2	Q9P227-1
ARHGAP23	ENST00000616767.2 linkuse as main transcript	c.1169G>A	p.Arg390Gln	missense_variant	7/24	3		ENSP00000516485	A2
ARHGAP23	ENST00000633445.2 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	7/24	3		ENSP00000516484	A2
ARHGAP23	ENST00000620417.4 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	7/25	5		ENSP00000482992	A2	Q9P227-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000107

AC:

AN:

93546

Hom.:

AF XY:

0.00

AC XY:

AN XY:

49148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000558

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000450

AC:

AN:

1332540

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

651652

show subpopulations

Gnomad4 AFR exome

AF:

0.0000332

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000190

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.827G>A (p.R276Q) alteration is located in exon 7 (coding exon 7) of the ARHGAP23 gene. This alteration results from a G to A substitution at nucleotide position 827, causing the arginine (R) at amino acid position 276 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

T;.

Eigen

Benign

0.0079

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.0087

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

Sift4G

Benign

0.093

T;T

Polyphen

0.028

B;D

Vest4

0.30

MutPred

0.13

Loss of methylation at R276 (P = 0.0238);Loss of methylation at R276 (P = 0.0238);

MVP

0.42

ClinPred

0.75

GERP RS

3.8

Varity_R

0.092

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over