11-110580241-C-T

Variant names:

• chr11-110580241-C-T
• rs771954026
• NM_001384657.1:c.2705G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001384657.1(ARHGAP20):​c.2705G>A​(p.Ser902Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARHGAP20 NM_001384657.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29733536).

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.2705G>A	p.Ser902Asn	missense	Exon 15 of 15	NP_001371586.1	Q9P2F6-1
	ARHGAP20	NM_020809.4		c.2705G>A	p.Ser902Asn	missense	Exon 16 of 16	NP_065860.2	Q9P2F6-1
	ARHGAP20	NM_001258415.2		c.2636G>A	p.Ser879Asn	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.2705G>A	p.Ser902Asn	missense	Exon 15 of 15	ENSP00000507405.1	Q9P2F6-1
	ARHGAP20	ENST00000260283.8	TSL:1	c.2705G>A	p.Ser902Asn	missense	Exon 16 of 16	ENSP00000260283.4	Q9P2F6-1
	ARHGAP20	ENST00000524756.5	TSL:1	c.2636G>A	p.Ser879Asn	missense	Exon 15 of 15	ENSP00000432076.1	Q9P2F6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

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

GnomAD4 genome Cov.: 32

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.21		Gain of sheet (P = 0.0101)
MVP		0.52
MPC		0.49
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.43
gMVP		0.45
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: rs771954026; hg19: chr11-110450965;