Variant 7-144187662-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000378115.3(ARHGEF35):c.722G>A(p.Arg241Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000061 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF35
ENST00000378115.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

ARHGEF35 (HGNC:33846): (Rho guanine nucleotide exchange factor 35)

ARHGEF35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02702123).

BP6

Variant 7-144187662-C-T is Benign according to our data. Variant chr7-144187662-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3129287.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3 linkuse as main transcript	c.722G>A	p.Arg241Gln	missense_variant	2/2	ENST00000378115.3	NP_001003702.2
ARHGEF35	NM_001368318.1 linkuse as main transcript	c.722G>A	p.Arg241Gln	missense_variant	2/2		NP_001355247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF35	ENST00000378115.3 linkuse as main transcript	c.722G>A	p.Arg241Gln	missense_variant	2/2	1	NM_001003702.3	ENSP00000367355	P1
ARHGEF35	ENST00000688754.1 linkuse as main transcript	c.722G>A	p.Arg241Gln	missense_variant	2/2			ENSP00000510684	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98484

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000193

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:

0.0000212

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000606

AC:

AN:

445748

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

234198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000826

Gnomad4 AMR exome

AF:

0.000212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000658

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000573

Gnomad4 OTH exome

AF:

0.000157

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000406

AC:

AN:

98536

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

46874

show subpopulations

Gnomad4 AFR

AF:

0.0000433

Gnomad4 AMR

AF:

0.000193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000212

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.18

DANN

Benign

0.58

DEOGEN2

Benign

0.0038

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.34

M_CAP

Benign

0.0016

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

2.0

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.013

MutPred

0.18

Gain of sheet (P = 0.0827);

MVP

0.040

MPC

1.3

ClinPred

0.038

GERP RS

-2.3

Varity_R

0.019

gMVP

0.0047

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