Variant 16-24939448-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006634.3(ARHGAP17):c.1640C>G(p.Ser547Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ARHGAP17
NM_001006634.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45

Variant links:

Genes affected

ARHGAP17 (HGNC:18239): (Rho GTPase activating protein 17) RICH1 is a GTPase-activating protein (GAP). GAPs stimulate the intrinsic GTP hydrolysis of small G proteins, such as RHOA (MIM 165390), RAC1 (MIM 602048), and CDC42 (MIM 116952).[supplied by OMIM, Apr 2004]

ARHGAP17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2567625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP17	NM_001006634.3 linkuse as main transcript	c.1640C>G	p.Ser547Cys	missense_variant	17/20	ENST00000289968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP17	ENST00000289968.11 linkuse as main transcript	c.1640C>G	p.Ser547Cys	missense_variant	17/20	1	NM_001006634.3	P3	Q68EM7-1
ARHGAP17	ENST00000303665.9 linkuse as main transcript	c.1490+2539C>G		intron_variant		1		A2	Q68EM7-2
ARHGAP17	ENST00000572314.5 linkuse as main transcript	n.3722C>G		non_coding_transcript_exon_variant	8/11	2
ARHGAP17	ENST00000575283.5 linkuse as main transcript	n.474C>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1459170

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000225

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:

0.0000279

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000340

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

Sep 17, 2021

The c.1640C>G (p.S547C) alteration is located in exon 17 (coding exon 17) of the ARHGAP17 gene. This alteration results from a C to G substitution at nucleotide position 1640, causing the serine (S) at amino acid position 547 to be replaced by a cysteine (C). 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

0.077

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

M_CAP

Benign

0.013

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

REVEL

Benign

0.089

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.30

MutPred

0.22

Loss of phosphorylation at S547 (P = 0.0016);

MVP

0.44

MPC

0.20

ClinPred

0.89

GERP RS

5.3

Varity_R

0.10

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over