rs3764653

Positions:

• chr19-1068735-T-A
• chr19-1068735-T-C

Variant summary

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

The NM_012292.5(ARHGAP45):​c.412T>A​(p.Leu138Met) 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. 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. Synonymous variant affecting the same amino acid position (i.e. L138L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP45 NM_012292.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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]

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=0.15594774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP45	NM_012292.5	c.412T>A	p.Leu138Met	missense_variant	2/23	ENST00000313093.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP45	ENST00000313093.7	c.412T>A	p.Leu138Met	missense_variant	2/23	1	NM_012292.5	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151476 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 40

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151476 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73912

Gnomad4 AFR AF: 0.00

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.010
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	0.84	D;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.85	N;.;N;.;.
REVEL	Benign	0.062
Sift	Uncertain	0.015	D;.;D;.;.
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.98	.;.;D;.;.
Vest4		0.36
MutPred		0.24		.;.;Gain of catalytic residue at L138 (P = 0.0309);.;.;
MVP		0.29
MPC		1.5
ClinPred		0.82	D
GERP RS		2.1
Varity_R		0.11
gMVP		0.31

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

Other links and lift over

dbSNP: rs3764653; hg19: chr19-1068734;