Genetic Variant NM_014786.4:c.193C>T (chr11-73308831-C-T) – 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.193C>T(p.Pro65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,188,148 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ARHGEF17
NM_014786.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0280

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=0.18539175).

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.193C>T	p.Pro65Ser	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.531G>A		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.193C>T	p.Pro65Ser	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
ARHGEF17	ENST00000914587.1		c.193C>T	p.Pro65Ser	missense	Exon 1 of 20	ENSP00000584647.1
ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.531G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

2098

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

AF:

0.00000421

AC:

AN:

1188148

Hom.:

Cov.:

AF XY:

0.00000523

AC XY:

AN XY:

573552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23420

American (AMR)

AF:

0.00

AC:

AN:

8974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16434

East Asian (EAS)

AF:

0.00

AC:

AN:

26962

South Asian (SAS)

AF:

0.00

AC:

AN:

47290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3340

European-Non Finnish (NFE)

AF:

0.00000508

AC:

AN:

984600

Other (OTH)

AF:

0.00

AC:

AN:

48820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.028

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.14

REVEL

Benign

0.042

Sift

Uncertain

0.0080

Sift4G

Benign

0.66

Polyphen

0.42

Vest4

0.22

MutPred

0.22

Gain of phosphorylation at P65 (P = 0.013)

MVP

0.34

MPC

0.42

ClinPred

0.28

GERP RS

2.6

Varity_R

0.053

gMVP

0.20

Mutation Taster

=95/5

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