Variant 11-73309093-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_014786.4(ARHGEF17):c.455G>A(p.Ser152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,394,802 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ARHGEF17
NM_014786.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.702

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity ARHGH_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11192095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF17	NM_014786.4 linkuse as main transcript	c.455G>A	p.Ser152Asn	missense_variant	1/21	ENST00000263674.4
ARHGEF17-AS1	NR_147696.1 linkuse as main transcript	n.269C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF17	ENST00000263674.4 linkuse as main transcript	c.455G>A	p.Ser152Asn	missense_variant	1/21	1	NM_014786.4	P1
ARHGEF17-AS1	ENST00000546324.1 linkuse as main transcript	n.269C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1394802

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689994

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:

0.00000554

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.455G>A (p.S152N) alteration is located in exon 1 (coding exon 1) of the ARHGEF17 gene. This alteration results from a G to A substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.019

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.88

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.12

REVEL

Benign

0.071

Sift

Benign

0.12

Sift4G

Benign

0.078

Polyphen

0.0

Vest4

0.14

MutPred

0.15

Loss of phosphorylation at S152 (P = 0.0042);

MVP

0.28

MPC

0.36

ClinPred

0.098

GERP RS

2.9

Varity_R

0.052

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over