11-110579954-C-A

Variant names:

• chr11-110579954-C-A
• rs1780612053
• NM_001384657.1:c.2992G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384657.1(ARHGAP20):​c.2992G>T​(p.Val998Phe) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARHGAP20 NM_001384657.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.845
• Publications: 0 publications found

Genes affected

ARHGAP20 (HGNC:18357): (Rho GTPase activating protein 20) The protein encoded by this gene is an activator of RHO-type GTPases, transducing a signal from RAP1 to RHO and impacting neurite outgrowth. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06428787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384657.1. 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
	ARHGAP20	NM_001384657.1	MANE Select	c.2992G>T	p.Val998Phe	missense	Exon 15 of 15	NP_001371586.1	Q9P2F6-1
	ARHGAP20	NM_020809.4		c.2992G>T	p.Val998Phe	missense	Exon 16 of 16	NP_065860.2	Q9P2F6-1
	ARHGAP20	NM_001258415.2		c.2923G>T	p.Val975Phe	missense	Exon 15 of 15	NP_001245344.1	Q9P2F6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP20	ENST00000683387.1	MANE Select	c.2992G>T	p.Val998Phe	missense	Exon 15 of 15	ENSP00000507405.1	Q9P2F6-1
	ARHGAP20	ENST00000260283.8	TSL:1	c.2992G>T	p.Val998Phe	missense	Exon 16 of 16	ENSP00000260283.4	Q9P2F6-1
	ARHGAP20	ENST00000524756.5	TSL:1	c.2923G>T	p.Val975Phe	missense	Exon 15 of 15	ENSP00000432076.1	Q9P2F6-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0050
DANN	Benign	0.83
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.84
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.031
Sift	Benign	0.30	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.11		Loss of sheet (P = 0.0457)
MVP		0.22
MPC		0.14
ClinPred		0.051	T
GERP RS		-8.3
Varity_R		0.051
gMVP		0.12
Mutation Taster		=82/18	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: rs1780612053; hg19: chr11-110450678;