Variant 3-154122048-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000465093.6(ARHGEF26):c.56G>T(p.Arg19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,500 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 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARHGEF26
ENST00000465093.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

ARHGEF26 (HGNC:24490): (Rho guanine nucleotide exchange factor 26) This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ARHGEF26 links:

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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=0.11335409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF26	NM_015595.4 linkuse as main transcript	c.56G>T	p.Arg19Leu	missense_variant	2/15	ENST00000465093.6	NP_056410.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF26	ENST00000465093.6 linkuse as main transcript	c.56G>T	p.Arg19Leu	missense_variant	2/15	1	NM_015595.4	ENSP00000423418	P1	Q96DR7-1
ARHGEF26	ENST00000465817.1 linkuse as main transcript	c.56G>T	p.Arg19Leu	missense_variant	2/5	1		ENSP00000423295		Q96DR7-3
ARHGEF26	ENST00000356448.8 linkuse as main transcript	c.56G>T	p.Arg19Leu	missense_variant	2/15	2		ENSP00000348828	P1	Q96DR7-1
ARHGEF26	ENST00000496710.5 linkuse as main transcript	c.56G>T	p.Arg19Leu	missense_variant	2/15	2		ENSP00000424446		Q96DR7-4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247148

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000582

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:

0.00000137

AC:

AN:

1459184

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 30, 2023

The c.56G>T (p.R19L) alteration is located in exon 2 (coding exon 1) of the ARHGEF26 gene. This alteration results from a G to T substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a leucine (L). 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

0.29

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

T;T;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

2.0

M;M;M;M

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

N;N;N;D

REVEL

Benign

0.088

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

0.80

P;P;.;.

Vest4

0.47

MutPred

0.53

Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);

MVP

0.53

MPC

0.11

ClinPred

0.73

GERP RS

3.8

Varity_R

0.39

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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