19-1073566-C-G

Variant names:

• chr19-1073566-C-G
• rs145027652
• NM_012292.5:c.626C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012292.5(ARHGAP45):​c.626C>G​(p.Thr209Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T209M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP45 NM_012292.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012292.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	NM_012292.5	MANE Select	c.626C>G	p.Thr209Arg	missense	Exon 4 of 23	NP_036424.2
	ARHGAP45	NM_001258328.4		c.674C>G	p.Thr225Arg	missense	Exon 4 of 23	NP_001245257.1	Q92619-2
	ARHGAP45	NM_001321232.2		c.638C>G	p.Thr213Arg	missense	Exon 4 of 23	NP_001308161.1	K7ES98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	ENST00000313093.7	TSL:1 MANE Select	c.626C>G	p.Thr209Arg	missense	Exon 4 of 23	ENSP00000316772.2	Q92619-1
	ARHGAP45	ENST00000586866.5	TSL:1	c.638C>G	p.Thr213Arg	missense	Exon 4 of 23	ENSP00000468615.1	K7ES98
	ARHGAP45	ENST00000885660.1		c.626C>G	p.Thr209Arg	missense	Exon 4 of 22	ENSP00000555719.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.44		Loss of ubiquitination at K205 (P = 0.0816)
MVP		0.53
MPC		1.8
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.69
gMVP		0.74
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs145027652; hg19: chr19-1073565;