19-1073566-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012292.5(ARHGAP45):​c.626C>T​(p.Thr209Met) variant causes a missense change. The variant allele was found at a frequency of 0.00032 in 1,613,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: ARHGAP45 NM_012292.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08127156).

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>T	p.Thr209Met	missense	Exon 4 of 23	NP_036424.2
	ARHGAP45	NM_001258328.4		c.674C>T	p.Thr225Met	missense	Exon 4 of 23	NP_001245257.1	Q92619-2
	ARHGAP45	NM_001321232.2		c.638C>T	p.Thr213Met	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>T	p.Thr209Met	missense	Exon 4 of 23	ENSP00000316772.2	Q92619-1
	ARHGAP45	ENST00000586866.5	TSL:1	c.638C>T	p.Thr213Met	missense	Exon 4 of 23	ENSP00000468615.1	K7ES98
	ARHGAP45	ENST00000885660.1		c.626C>T	p.Thr209Met	missense	Exon 4 of 22	ENSP00000555719.1

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 67 AN: 152082 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000195 AC: 49 AN: 250810 AF XY: 0.000184

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000307 AC: 449 AN: 1461668 Hom.: 0 Cov.: 34 AF XY: 0.000329 AC XY: 239 AN XY: 727132

African (AFR) AF: 0.000986 AC: 33 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000358 AC: 398 AN: 1111900

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152200 Hom.: 1 Cov.: 33 AF XY: 0.000417 AC XY: 31 AN XY: 74416

African (AFR) AF: 0.00116 AC: 48 AN: 41508

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000303 Hom.: 0

Bravo AF: 0.000502

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000181 AC: 22

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.45
MVP		0.53
MPC		1.3
ClinPred		0.14	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.55
Mutation Taster		=78/22	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;