rs868093634

Variant names:

• chr4-85570665-G-C
• rs868093634
• NM_001025616.3:c.124G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-85570665-G-C
• chr4-85570665-G-A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001025616.3(ARHGAP24):​c.124G>C​(p.Val42Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ARHGAP24 NM_001025616.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 9.92
• Publications: 0 publications found

Genes affected

ARHGAP24 (HGNC:25361): (Rho GTPase activating protein 24) This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ARHGAP24 Gene-Disease associations (from GenCC):

• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025616.3. 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
	ARHGAP24	NM_001025616.3	MANE Select	c.124G>C	p.Val42Leu	missense	Exon 2 of 10	NP_001020787.2	Q8N264-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP24	ENST00000395184.6	TSL:2 MANE Select	c.124G>C	p.Val42Leu	missense	Exon 2 of 10	ENSP00000378611.1	Q8N264-1
	ARHGAP24	ENST00000503995.5	TSL:1	c.124G>C	p.Val42Leu	missense	Exon 2 of 6	ENSP00000423206.1	Q8N264-4
	ARHGAP24	ENST00000505856.1	TSL:2	n.218G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		9.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.76
MutPred		0.71		Loss of methylation at K44 (P = 0.0524)
MVP		0.70
MPC		0.50
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.69
gMVP		0.52
Mutation Taster		=55/45	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: rs868093634; hg19: chr4-86491818;