rs377326713
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001353921.2(ARHGEF9):c.254A>T(p.Asp85Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000332 in 1,205,515 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D85N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001353921.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.254A>T | p.Asp85Val | missense_variant | 3/10 | ENST00000671741.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.254A>T | p.Asp85Val | missense_variant | 3/10 | NM_001353921.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111481Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33653
GnomAD3 exomes AF: 0.00000581 AC: 1AN: 172005Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 57971
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1094034Hom.: 0 Cov.: 31 AF XY: 0.00000556 AC XY: 2AN XY: 359992
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111481Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33653
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 78 of the ARHGEF9 protein (p.Asp78Val). ClinVar contains an entry for this variant (Variation ID: 581455). This variant has not been reported in the literature in individuals affected with ARHGEF9-related conditions. This variant is present in population databases (rs377326713, gnomAD 0.003%), including at least one homozygous and/or hemizygous individual. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ARHGEF9 protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at