rs771840583

Variant summary

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

The NM_001242729.2(ARHGEF38):​c.479C>G​(p.Thr160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T160I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ARHGEF38
NM_001242729.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.17651016).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGEF38NM_001242729.2 linkc.479C>G p.Thr160Arg missense_variant Exon 3 of 14 ENST00000420470.3 NP_001229658.1 Q9NXL2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGEF38ENST00000420470.3 linkc.479C>G p.Thr160Arg missense_variant Exon 3 of 14 5 NM_001242729.2 ENSP00000416125.2 Q9NXL2-2
ARHGEF38ENST00000265154.6 linkc.479C>G p.Thr160Arg missense_variant Exon 3 of 4 1 ENSP00000265154.2 Q9NXL2-1
ARHGEF38ENST00000506828.1 linkn.352C>G non_coding_transcript_exon_variant Exon 3 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460832
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726696
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0079
.;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;M
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.10
Sift
Benign
0.13
T;T
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.38
.;B
Vest4
0.38
MutPred
0.40
Gain of solvent accessibility (P = 0.0503);Gain of solvent accessibility (P = 0.0503);
MVP
0.21
MPC
0.16
ClinPred
0.87
D
GERP RS
4.8
Varity_R
0.36
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs771840583; hg19: chr4-106534635; API