16-24939434-T-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.1654A>G(p.Ser552Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 (0 hom.)
• Consequence: ARHGAP17 NM_001006634.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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=0.10086891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP17	NM_001006634.3	c.1654A>G	p.Ser552Gly	missense_variant	17/20	ENST00000289968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP17	ENST00000289968.11	c.1654A>G	p.Ser552Gly	missense_variant	17/20	1	NM_001006634.3	P3
ARHGAP17	ENST00000303665.9	c.1490+2553A>G		intron_variant		1		A2
ARHGAP17	ENST00000572314.5	n.3736A>G		non_coding_transcript_exon_variant	8/11	2
ARHGAP17	ENST00000575283.5	n.488A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459836 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726134

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: 0.00

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

Jul 25, 2023

The c.1654A>G (p.S552G) alteration is located in exon 17 (coding exon 17) of the ARHGAP17 gene. This alteration results from a A to G substitution at nucleotide position 1654, causing the serine (S) at amino acid position 552 to be replaced by a glycine (G). 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	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.0043
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.50	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.034
Sift	Benign	0.068	T
Sift4G	Benign	0.29	T
Polyphen		0.49	P
Vest4		0.14
MutPred		0.17		Loss of phosphorylation at S552 (P = 0.0067);
MVP		0.47
MPC		0.044
ClinPred		0.30	T
GERP RS		4.2
Varity_R		0.052
gMVP		0.13

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: chr16-24950755;