chr11-110580559-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384657.1(ARHGAP20):ā€‹c.2387C>Gā€‹(p.Ser796Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,110 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

ARHGAP20
NM_001384657.1 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10151416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARHGAP20NM_001384657.1 linkuse as main transcriptc.2387C>G p.Ser796Cys missense_variant 15/15 ENST00000683387.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP20ENST00000683387.1 linkuse as main transcriptc.2387C>G p.Ser796Cys missense_variant 15/15 NM_001384657.1 P4Q9P2F6-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251320
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000893
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461888
Hom.:
0
Cov.:
33
AF XY:
0.0000193
AC XY:
14
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000803
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000217
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022The c.2387C>G (p.S796C) 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 2387, causing the serine (S) at amino acid position 796 to be replaced by a cysteine (C). 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
0.098
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;T;.;.;.;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.88
D;D;D;.;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.10
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.1
M;.;.;.;.;.
MutationTaster
Benign
0.95
N;N;N;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0010
D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;D;.
Vest4
0.30
MutPred
0.32
Loss of loop (P = 9e-04);.;.;.;.;.;
MVP
0.51
MPC
0.53
ClinPred
0.57
D
GERP RS
4.5
Varity_R
0.18
gMVP
0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202088486; hg19: chr11-110451283; API