chr11-110579779-G-C

Variant names:

• chr11-110579779-G-C
• NM_001384657.1:c.3167C>G

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.3167C>G​(p.Ala1056Gly) 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. 14/22 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)
• Consequence: ARHGAP20 NM_001384657.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• 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=0.06702712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP20	NM_001384657.1	c.3167C>G	p.Ala1056Gly	missense_variant	Exon 15 of 15	ENST00000683387.1	NP_001371586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP20	ENST00000683387.1	c.3167C>G	p.Ala1056Gly	missense_variant	Exon 15 of 15		NM_001384657.1	ENSP00000507405.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3167C>G (p.A1056G) alteration is located in exon 16 (coding exon 15) of the ARHGAP20 gene. This alteration results from a C to G substitution at nucleotide position 3167, causing the alanine (A) at amino acid position 1056 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T;T;.;.;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.83	T;T;T;.;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.067	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.
PhyloP100		1.6
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D
Polyphen		0.22	B;.;B;.;B;.
Vest4		0.14
MutPred		0.13		Gain of loop (P = 0.069);.;.;.;.;.;
MVP		0.36
MPC		0.20
ClinPred		0.73	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.13
Mutation Taster		=95/5	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

hg19: chr11-110450503;