rs1057520158
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001353921.2(ARHGEF9):c.1148T>C(p.Ile383Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I383M) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 22)
Consequence
ARHGEF9
NM_001353921.2 missense
NM_001353921.2 missense
Scores
10
7
Clinical Significance
Conservation
PhyloP100: 4.48
Genes affected
ARHGEF9 (HGNC:14561): (Cdc42 guanine nucleotide exchange factor 9) The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.1148T>C | p.Ile383Thr | missense_variant | 8/10 | ENST00000671741.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.1148T>C | p.Ile383Thr | missense_variant | 8/10 | NM_001353921.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 13, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.;T;T;T;T;T;T;.;.;T;.;T;T;.;T;.;T;T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;D;.;.;.;D;D;.;D;.;.;D;.;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.
Sift4G
Benign
T;T;T;.;.;.;.;.;.;T;T;T;.;.;.;.;T;T;.;.;.
Polyphen
B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0197);.;Gain of disorder (P = 0.0197);.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;Gain of disorder (P = 0.0197);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at