Variant 11-100948492-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152432.4(ARHGAP42):c.1079C>T(p.Ala360Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000858 in 1,397,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ARHGAP42
NM_152432.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.93

Variant links:

Genes affected

ARHGAP42 (HGNC:26545): (Rho GTPase activating protein 42) This gene encodes a Rho GTPase-activating protein (RhoGAP), and member of the GRAF or BAR-PH family of proteins. Expression of this gene is enriched in vascular smooth muscle cells and the encoded protein inhibits RhoA activity to regulate vascular tone and control blood pressure. A mutation in the first intron of this gene modulates its expression and is associated with reduced blood pressure in human patients with borderline hypertension. [provided by RefSeq, Jul 2017]

ARHGAP42 links:

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ACMG classification

Classification made for transcript

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=0.22753471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP42	NM_152432.4 linkuse as main transcript	c.1079C>T	p.Ala360Val	missense_variant	11/24	ENST00000298815.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGAP42	ENST00000298815.13 linkuse as main transcript	c.1079C>T	p.Ala360Val	missense_variant	11/24	5	NM_152432.4	P1
ARHGAP42	ENST00000524892.7 linkuse as main transcript	c.977C>T	p.Ala326Val	missense_variant	10/23	5
ARHGAP42	ENST00000531183.1 linkuse as main transcript	c.647C>T	p.Ala216Val	missense_variant	7/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

157366

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1397932

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000378

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

Jun 23, 2023

The c.1079C>T (p.A360V) alteration is located in exon 11 (coding exon 11) of the ARHGAP42 gene. This alteration results from a C to T substitution at nucleotide position 1079, causing the alanine (A) at amino acid position 360 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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.44

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.089

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.078

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.25

MutPred

0.41

.;Gain of helix (P = 0.2059);.;

MVP

0.18

ClinPred

0.48

GERP RS

5.7

Varity_R

0.10

gMVP

0.46

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