Variant 3-154122026-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000465093.6(ARHGEF26):c.34A>G(p.Asn12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ARHGEF26
ENST00000465093.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.911

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061802268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF26	NM_015595.4 linkuse as main transcript	c.34A>G	p.Asn12Asp	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.34A>G	p.Asn12Asp	missense_variant	2/15	1	NM_015595.4	ENSP00000423418	P1	Q96DR7-1
ARHGEF26	ENST00000465817.1 linkuse as main transcript	c.34A>G	p.Asn12Asp	missense_variant	2/5	1		ENSP00000423295		Q96DR7-3
ARHGEF26	ENST00000356448.8 linkuse as main transcript	c.34A>G	p.Asn12Asp	missense_variant	2/15	2		ENSP00000348828	P1	Q96DR7-1
ARHGEF26	ENST00000496710.5 linkuse as main transcript	c.34A>G	p.Asn12Asp	missense_variant	2/15	2		ENSP00000424446		Q96DR7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000283

AC:

AN:

247206

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000484

AC:

AN:

1445748

Hom.:

Cov.:

AF XY:

0.00000699

AC XY:

AN XY:

715520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

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

Jan 25, 2023

The c.34A>G (p.N12D) alteration is located in exon 2 (coding exon 1) of the ARHGEF26 gene. This alteration results from a A to G substitution at nucleotide position 34, causing the asparagine (N) at amino acid position 12 to be replaced by an aspartic acid (D). 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

0.069

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0034

T;T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.67

.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;L

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.031

D;D;D;D

Sift4G

Benign

0.75

T;T;T;T

Polyphen

0.0080

B;B;.;.

Vest4

0.10

MutPred

0.23

Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);

MVP

0.34

MPC

0.092

ClinPred

0.039

GERP RS

1.9

Varity_R

0.13

gMVP

0.17

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