14-32091391-C-T

Position:

• chr14-32091391-C-T

Variant summary

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

The NM_001030055.2(ARHGAP5):​c.722C>T​(p.Ala241Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP5 NM_001030055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

ARHGAP5 (HGNC:675): (Rho GTPase activating protein 5) Rho GTPase activating protein 5 negatively regulates RHO GTPases, a family which may mediate cytoskeleton changes by stimulating the hydrolysis of bound GTP. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP5	NM_001030055.2	c.722C>T	p.Ala241Val	missense_variant	2/7	ENST00000345122.8	NP_001025226.1
ARHGAP5	NM_001173.3	c.722C>T	p.Ala241Val	missense_variant	2/7		NP_001164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP5	ENST00000345122.8	c.722C>T	p.Ala241Val	missense_variant	2/7	5	NM_001030055.2	ENSP00000371897	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Oct 25, 2023

The c.722C>T (p.A241V) alteration is located in exon 2 (coding exon 1) of the ARHGAP5 gene. This alteration results from a C to T substitution at nucleotide position 722, causing the alanine (A) at amino acid position 241 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.26	.;T;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.85	L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.87	N;N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.85	T;T;T;T
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.87	P;P;.;P
Vest4		0.69
MutPred		0.74		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.69
MPC		0.68
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.44

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: chr14-32560597;