chr16-24931156-G-A

Position:

• chr16-24931156-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001006634.3(ARHGAP17):​c.2143C>T​(p.Pro715Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,850 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARHGAP17 NM_001006634.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.00

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3862584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP17	NM_001006634.3	c.2143C>T	p.Pro715Ser	missense_variant	19/20	ENST00000289968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP17	ENST00000289968.11	c.2143C>T	p.Pro715Ser	missense_variant	19/20	1	NM_001006634.3	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447850 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 719034

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: 0.0000239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jun 21, 2022

The c.2143C>T (p.P715S) alteration is located in exon 19 (coding exon 19) of the ARHGAP17 gene. This alteration results from a C to T substitution at nucleotide position 2143, causing the proline (P) at amino acid position 715 to be replaced by a serine (S). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.75
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.94	P;P
Vest4		0.38
MutPred		0.33		Loss of catalytic residue at P715 (P = 0.0081);.;
MVP		0.57
MPC		0.19
ClinPred		0.91	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.29

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: chr16-24942477;