NM_014786.4:c.269A>G

Variant summary

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

The NM_014786.4(ARHGEF17):​c.269A>G​(p.Asp90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,361,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ARHGEF17
NM_014786.4 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96
Variant links:
Genes affected
ARHGEF17 (HGNC:21726): (Rho guanine nucleotide exchange factor 17) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

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=0.25329125).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGEF17NM_014786.4 linkc.269A>G p.Asp90Gly missense_variant Exon 1 of 21 ENST00000263674.4 NP_055601.2 Q96PE2
ARHGEF17-AS1NR_147696.1 linkn.455T>C non_coding_transcript_exon_variant Exon 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGEF17ENST00000263674.4 linkc.269A>G p.Asp90Gly missense_variant Exon 1 of 21 1 NM_014786.4 ENSP00000263674.3 Q96PE2
ARHGEF17-AS1ENST00000546324.1 linkn.455T>C non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151732
Hom.:
0
Cov.:
33
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:
0.000195
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000413
AC:
5
AN:
1209896
Hom.:
0
Cov.:
30
AF XY:
0.00000170
AC XY:
1
AN XY:
586536
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000185
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151846
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000196
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.269A>G (p.D90G) alteration is located in exon 1 (coding exon 1) of the ARHGEF17 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the aspartic acid (D) at amino acid position 90 to be replaced by a glycine (G). 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
0.12
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.53
T
M_CAP
Pathogenic
0.84
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.81
L
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.43
N
REVEL
Benign
0.054
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.087
T
Polyphen
0.43
B
Vest4
0.42
MutPred
0.16
Gain of MoRF binding (P = 0.0359);
MVP
0.46
MPC
1.4
ClinPred
0.51
D
GERP RS
2.1
Varity_R
0.14
gMVP
0.25

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: rs1446796685; hg19: chr11-73019952; API