rs782187939
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001353921.2(ARHGEF9):c.564A>T(p.Gly188Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,096,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )
Consequence
ARHGEF9
NM_001353921.2 synonymous
NM_001353921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.574
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant X-63697143-T-A is Benign according to our data. Variant chrX-63697143-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 389944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.574 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000456 (5/1096791) while in subpopulation SAS AF= 0.0000742 (4/53875). AF 95% confidence interval is 0.0000253. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.564A>T | p.Gly188Gly | synonymous_variant | 4/10 | ENST00000671741.2 | NP_001340850.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.564A>T | p.Gly188Gly | synonymous_variant | 4/10 | NM_001353921.2 | ENSP00000500715.1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
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22
GnomAD3 exomes AF: 0.0000279 AC: 5AN: 179299Hom.: 0 AF XY: 0.0000311 AC XY: 2AN XY: 64345
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GnomAD4 exome AF: 0.00000456 AC: 5AN: 1096791Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 2AN XY: 362539
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GnomAD4 genome Cov.: 22
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Developmental and epileptic encephalopathy, 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at