NM_032496.4:c.745C>G

Variant names:

• chr12-57477470-G-C
• NM_032496.4:c.745C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032496.4(ARHGAP9):​c.745C>G​(p.Arg249Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARHGAP9 NM_032496.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

ARHGAP9 (HGNC:14130): (Rho GTPase activating protein 9) This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

ACMG classification

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=0.1859689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP9	NM_032496.4	c.745C>G	p.Arg249Gly	missense_variant	Exon 4 of 18	ENST00000393791.8	NP_115885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP9	ENST00000393791.8	c.745C>G	p.Arg249Gly	missense_variant	Exon 4 of 18	1	NM_032496.4	ENSP00000377380.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461778 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	.;.;.;T;.;T;T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.81	T;T;T;.;T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M;M;.;.;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N;N;.;N;D;N;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;D;D;.;D;D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D;T;.;.;D;.
Polyphen		0.65	P;.;.;.;.;.;.;.;.
Vest4		0.39
MutPred		0.33		Gain of catalytic residue at P245 (P = 5e-04);Gain of catalytic residue at P245 (P = 5e-04);.;.;.;.;.;.;.;
MVP		0.72
MPC		0.086
ClinPred		0.72	D
GERP RS		3.6
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-57871253;