16-24939389-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001006634.3(ARHGAP17):c.1699C>G(p.Gln567Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,562 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ARHGAP17 NM_001006634.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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]

ACMG classification

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=0.18792444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP17	NM_001006634.3	c.1699C>G	p.Gln567Glu	missense_variant	17/20	ENST00000289968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP17	ENST00000289968.11	c.1699C>G	p.Gln567Glu	missense_variant	17/20	1	NM_001006634.3	P3
ARHGAP17	ENST00000303665.9	c.1490+2598C>G		intron_variant		1		A2
ARHGAP17	ENST00000572314.5	n.3781C>G		non_coding_transcript_exon_variant	8/11	2
ARHGAP17	ENST00000575283.5	n.533C>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456562 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724472

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2023

The c.1699C>G (p.Q567E) 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 1699, causing the glutamine (Q) at amino acid position 567 to be replaced by a glutamic acid (E). 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	0.074
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.098
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Polyphen		0.29	B
Vest4		0.31
MutPred		0.21		Gain of catalytic residue at Q567 (P = 0.0522);
MVP		0.66
MPC		0.050
ClinPred		0.28	T
GERP RS		5.3
Varity_R		0.090
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-24950710;