Genetic Variant ARHGEF35:p.Gly467Val (chr7-144186984-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003702.3(ARHGEF35):c.1400G>T(p.Gly467Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 143,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G467D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 21)

Consequence

ARHGEF35
NM_001003702.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.755

Publications

0 publications found

Variant links:

Genes affected

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

ARHGEF35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15424353).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003702.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF35	NM_001003702.3	MANE Select	c.1400G>T	p.Gly467Val	missense	Exon 2 of 2	NP_001003702.2	A5YM69
	ARHGEF35	NM_001368318.1		c.1400G>T	p.Gly467Val	missense	Exon 2 of 2	NP_001355247.1	A5YM69

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGEF35	ENST00000378115.3	TSL:1 MANE Select	c.1400G>T	p.Gly467Val	missense	Exon 2 of 2	ENSP00000367355.3	A5YM69
ARHGEF35	ENST00000688754.1		c.1400G>T	p.Gly467Val	missense	Exon 2 of 2	ENSP00000510684.1	A5YM69
ARHGEF35	ENST00000852510.1		c.1400G>T	p.Gly467Val	missense	Exon 3 of 3	ENSP00000522569.1

Frequencies

GnomAD3 genomes

AF:

0.00000696

AC:

AN:

143688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

239266

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000696

AC:

AN:

143688

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

70074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38802

American (AMR)

AF:

0.00

AC:

AN:

14686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

64040

Other (OTH)

AF:

0.00

AC:

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000169

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.7

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.80

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.47

M_CAP

Benign

0.0039

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.76

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.13

Sift

Uncertain

0.024

Sift4G

Benign

0.20

Polyphen

0.95

Vest4

0.10

MutPred

0.27

Gain of sheet (P = 0.0061)

MVP

0.13

MPC

1.7

ClinPred

0.32

GERP RS

-2.0

Varity_R

0.099

gMVP

0.015

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over