Genetic Variant NM_018287.7:c.1325T>A (chr10-31839683-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018287.7(ARHGAP12):c.1325T>A(p.Phe442Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARHGAP12
NM_018287.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Publications

31 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04197052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018287.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP12	NM_018287.7	MANE Select	c.1325T>A	p.Phe442Tyr	missense	Exon 8 of 20	NP_060757.4
ARHGAP12	NM_001270695.1		c.1325T>A	p.Phe442Tyr	missense	Exon 8 of 19	NP_001257624.1	Q8IWW6-4
ARHGAP12	NM_001270697.1		c.1184T>A	p.Phe395Tyr	missense	Exon 7 of 19	NP_001257626.1	Q1RLN5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP12	ENST00000344936.7	TSL:1 MANE Select	c.1325T>A	p.Phe442Tyr	missense	Exon 8 of 20	ENSP00000345808.2	Q8IWW6-1
ARHGAP12	ENST00000396144.8	TSL:1	c.1325T>A	p.Phe442Tyr	missense	Exon 8 of 19	ENSP00000379448.4	Q8IWW6-4
ARHGAP12	ENST00000375245.8	TSL:1	c.1184T>A	p.Phe395Tyr	missense	Exon 7 of 19	ENSP00000364394.5	Q1RLN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723838

African (AFR)

AF:

0.00

AC:

AN:

33382

American (AMR)

AF:

0.00

AC:

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39410

South Asian (SAS)

AF:

0.00

AC:

AN:

85478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107326

Other (OTH)

AF:

0.00

AC:

AN:

60062

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.017

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.54

M_CAP

Benign

0.0038

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

2.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.090

REVEL

Benign

0.037

Sift

Benign

1.0

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.20

MutPred

0.12

Gain of phosphorylation at F442 (P = 0.0388)

MVP

0.37

MPC

0.21

ClinPred

0.20

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.11

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over