Genetic Variant ARHGEF17:p.Ala68Pro (chr11-73308840-G-C) – 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_014786.4(ARHGEF17):c.202G>C(p.Ala68Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000845 in 1,182,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A68T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

ARHGEF17
NM_014786.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.412

Publications

0 publications found

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 links:

ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

ARHGEF17-AS1 links:

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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=0.14905542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014786.4. 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
	ARHGEF17	NM_014786.4	MANE Select	c.202G>C	p.Ala68Pro	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.522C>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGEF17	ENST00000263674.4	TSL:1 MANE Select	c.202G>C	p.Ala68Pro	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
ARHGEF17	ENST00000914587.1		c.202G>C	p.Ala68Pro	missense	Exon 1 of 20	ENSP00000584647.1
ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.522C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.45e-7

AC:

AN:

1182952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

570752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23376

American (AMR)

AF:

0.00

AC:

AN:

8904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16334

East Asian (EAS)

AF:

0.00

AC:

AN:

26946

South Asian (SAS)

AF:

0.00

AC:

AN:

45940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3336

European-Non Finnish (NFE)

AF:

0.00000102

AC:

AN:

981458

Other (OTH)

AF:

0.00

AC:

AN:

48468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

0.41

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.080

REVEL

Benign

0.060

Sift

Pathogenic

0.0

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.22

MutPred

0.32

Gain of catalytic residue at A68 (P = 0.0067)

MVP

0.44

MPC

0.77

ClinPred

0.34

GERP RS

0.47

Varity_R

0.23

gMVP

0.33

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over