Variant 10-31839676-T-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_018287.7(ARHGAP12):c.1332A>C(p.Glu444Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARHGAP12
NM_018287.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

ARHGAP12 (HGNC:16348): (Rho GTPase activating protein 12) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may be involved in suppressing tumor formation by regulating cell invasion and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ARHGAP12 links:

ARHGAP12 (HGNC:):

ARHGAP12 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=0.16703624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP12	NM_018287.7 linkuse as main transcript	c.1332A>C	p.Glu444Asp	missense_variant	8/20	ENST00000344936.7	NP_060757.4	Q8IWW6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP12	ENST00000344936.7 linkuse as main transcript	c.1332A>C	p.Glu444Asp	missense_variant	8/20	1	NM_018287.7	ENSP00000345808.2		Q8IWW6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456946

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Sep 02, 2024

The c.1332A>C (p.E444D) alteration is located in exon 8 (coding exon 6) of the ARHGAP12 gene. This alteration results from a A to C substitution at nucleotide position 1332, causing the glutamic acid (E) at amino acid position 444 to be replaced by an aspartic acid (D). 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

0.081

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

.;.;.;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.46

.;N;.;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.17

N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.31

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0020, 0.0010

.;.;B;B

Vest4

0.46

MutPred

0.12

.;Loss of catalytic residue at E444 (P = 0.1125);.;Loss of catalytic residue at E444 (P = 0.1125);

MVP

0.51

MPC

0.17

ClinPred

0.54

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over