chrX-63637846-C-CTGTGTG
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001353921.2(ARHGEF9):c.*176_*181dupCACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000082 ( 0 hom., 2 hem., cov: 12)
Exomes 𝑓: 0.00044 ( 0 hom. 6 hem. )
Consequence
ARHGEF9
NM_001353921.2 3_prime_UTR
NM_001353921.2 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.87
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 Likely_benign. Variant got -4 ACMG points.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.*176_*181dupCACACA | 3_prime_UTR_variant | Exon 10 of 10 | ENST00000671741.2 | NP_001340850.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741 | c.*176_*181dupCACACA | 3_prime_UTR_variant | Exon 10 of 10 | NM_001353921.2 | ENSP00000500715.1 |
Frequencies
GnomAD3 genomes AF: 0.0000825 AC: 8AN: 97026Hom.: 0 Cov.: 12 AF XY: 0.0000842 AC XY: 2AN XY: 23766
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GnomAD4 exome AF: 0.000440 AC: 94AN: 213442Hom.: 0 Cov.: 0 AF XY: 0.0000943 AC XY: 6AN XY: 63622
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GnomAD4 genome AF: 0.0000824 AC: 8AN: 97040Hom.: 0 Cov.: 12 AF XY: 0.0000841 AC XY: 2AN XY: 23790
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at