Variant 1-94177653-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004815.4(ARHGAP29):c.2864G>A(p.Arg955His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,613,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

ARHGAP29
NM_004815.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

ARHGAP29 (HGNC:30207): (Rho GTPase activating protein 29) Rap1 is a small GTPase that, through effectors, regulates Rho GTPase signaling. These effectors- Rasip1, Radil, and the protein encoded by this gene- translocate to the cell membrane, where they form a multiprotein complex. This complex is necessary for Rap1-induced inhibition of Rho signaling. Defects in this gene may be a cause of nonsyndromic cleft lip with or without cleft palate. [provided by RefSeq, Jun 2016]

ARHGAP29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019516647).

BS2

High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4 linkuse as main transcript	c.2864G>A	p.Arg955His	missense_variant	22/23	ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11 linkuse as main transcript	c.2864G>A	p.Arg955His	missense_variant	22/23	1	NM_004815.4	P1	Q52LW3-1
ARHGAP29	ENST00000482481.1 linkuse as main transcript	n.7440G>A		non_coding_transcript_exon_variant	10/10	1
ARHGAP29	ENST00000552844.5 linkuse as main transcript	c.2864G>A	p.Arg955His	missense_variant, NMD_transcript_variant	22/26	1

Frequencies

GnomAD3 genomes

AF:

0.000882

AC:

134

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00491

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000502

AC:

126

AN:

250834

Hom.:

AF XY:

0.000465

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000233

AC:

340

AN:

1461194

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000888

AC:

135

AN:

152026

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00249

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00491

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000348

Hom.:

Bravo

AF:

0.00110

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.000219

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARHGAP29-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 17, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.023

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.76

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

1.0

REVEL

Benign

0.051

Sift

Benign

0.24

Sift4G

Benign

0.31

Polyphen

0.0030

Vest4

0.084

MVP

0.093

MPC

0.17

ClinPred

0.016

GERP RS

-1.3

Varity_R

0.033

gMVP

0.24

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