Variant 11-100948458-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.1045C>T(p.His349Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000602 in 1,544,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

ARHGAP42
NM_152432.4 missense, splice_region

Scores

Splicing: ADA: 0.9687

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

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=0.26112202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP42	NM_152432.4 linkuse as main transcript	c.1045C>T	p.His349Tyr	missense_variant, splice_region_variant	11/24	ENST00000298815.13	NP_689645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARHGAP42	ENST00000298815.13 linkuse as main transcript	c.1045C>T	p.His349Tyr	missense_variant, splice_region_variant	11/24	5	NM_152432.4	ENSP00000298815	P1
ARHGAP42	ENST00000524892.7 linkuse as main transcript	c.943C>T	p.His315Tyr	missense_variant, splice_region_variant	10/23	5		ENSP00000431776
ARHGAP42	ENST00000531183.1 linkuse as main transcript	c.613C>T	p.His205Tyr	missense_variant, splice_region_variant	7/7	3		ENSP00000434304

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000193

AC:

AN:

155342

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82160

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000332

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000632

AC:

AN:

1392410

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

686908

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

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:

0.0000772

Gnomad4 OTH exome

AF:

0.0000694

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000529

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

Nov 13, 2023

The c.1045C>T (p.H349Y) 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 1045, causing the histidine (H) at amino acid position 349 to be replaced by a tyrosine (Y). 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

Benign

-0.096

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.043

D;D;D

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0040

.;B;.

Vest4

0.34

MVP

0.081

ClinPred

0.23

GERP RS

5.7

Varity_R

0.13

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.010

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