Variant 19-1083343-C-G 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_012292.5(ARHGAP45):c.2945C>G(p.Pro982Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,548,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ARHGAP45
NM_012292.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

ARHGAP45 (HGNC:17102): (Rho GTPase activating protein 45) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP45 links:

ARHGAP45 (HGNC:):

ARHGAP45 links:

Genome browser will be placed here

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=0.07800025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 linkuse as main transcript	c.2945C>G	p.Pro982Arg	missense_variant	21/23	ENST00000313093.7	NP_036424.2	Q92619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7 linkuse as main transcript	c.2945C>G	p.Pro982Arg	missense_variant	21/23	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000265

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000116

AC:

AN:

154832

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

82824

show subpopulations

Gnomad AFR exome

AF:

0.000117

Gnomad AMR exome

AF:

0.0000395

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:

0.000241

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.000153

AC:

214

AN:

1396806

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

107

AN XY:

689784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000628

Gnomad4 AMR exome

AF:

0.0000822

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:

0.000184

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.000131

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000265

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000636

AC:

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

Aug 10, 2021

The c.2945C>G (p.P982R) alteration is located in exon 21 (coding exon 21) of the ARHGAP45 gene. This alteration results from a C to G substitution at nucleotide position 2945, causing the proline (P) at amino acid position 982 to be replaced by an arginine (R). 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

0.069

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.48

DEOGEN2

Benign

0.043

.;T;.;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.85

D;D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.078

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L;.;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.4

N;N;.;.;N;.

REVEL

Benign

0.018

Sift

Uncertain

0.018

D;D;.;.;T;.

Sift4G

Benign

0.29

T;T;T;T;T;T

Polyphen

0.31, 0.43

.;B;.;.;B;.

Vest4

0.14

MVP

0.072

MPC

0.013

ClinPred

0.039

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.43

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