10-31839683-A-T

Position:

• chr10-31839683-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F442S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP12 NM_018287.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04197052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP12	NM_018287.7	c.1325T>A	p.Phe442Tyr	missense_variant	8/20	ENST00000344936.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP12	ENST00000344936.7	c.1325T>A	p.Phe442Tyr	missense_variant	8/20	1	NM_018287.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723838

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.017	.;.;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.54	T;T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.042	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	.;L;.;L
MutationTaster	Benign	0.98	P;P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.090	N;N;N;N
REVEL	Benign	0.037
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.0	.;.;B;B
Vest4		0.20
MutPred		0.12		.;Gain of phosphorylation at F442 (P = 0.0388);.;Gain of phosphorylation at F442 (P = 0.0388);
MVP		0.37
MPC		0.21
ClinPred		0.20	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs2808096; hg19: chr10-32128611;