chr7-144187438-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001003702.3(ARHGEF35):​c.946G>T​(p.Gly316Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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. G316R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 15)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ARHGEF35
NM_001003702.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810
Variant links:
Genes affected
ARHGEF35 (HGNC:33846): (Rho guanine nucleotide exchange factor 35)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1616031).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGEF35NM_001003702.3 linkc.946G>T p.Gly316Cys missense_variant Exon 2 of 2 ENST00000378115.3 NP_001003702.2 A5YM69
ARHGEF35NM_001368318.1 linkc.946G>T p.Gly316Cys missense_variant Exon 2 of 2 NP_001355247.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGEF35ENST00000378115.3 linkc.946G>T p.Gly316Cys missense_variant Exon 2 of 2 1 NM_001003702.3 ENSP00000367355.3 A5YM69
ARHGEF35ENST00000688754.1 linkc.946G>T p.Gly316Cys missense_variant Exon 2 of 2 ENSP00000510684.1 A5YM69

Frequencies

GnomAD3 genomes
Cov.:
15
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000109
AC:
1
AN:
915382
Hom.:
0
Cov.:
15
AF XY:
0.00
AC XY:
0
AN XY:
466410
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:
0.00000152
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
12
DANN
Benign
0.81
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PROVEAN
Uncertain
-4.1
D
REVEL
Benign
0.047
Sift
Uncertain
0.022
D
Sift4G
Uncertain
0.048
D
Polyphen
1.0
D
Vest4
0.14
MutPred
0.19
Loss of relative solvent accessibility (P = 0.0071);
MVP
0.30
MPC
1.2
ClinPred
0.70
D
GERP RS
-3.4
Varity_R
0.31
gMVP
0.0085

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.

Other links and lift over

dbSNP: rs996964688; hg19: chr7-143884531; API