rs75329154
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004840.3(ARHGEF6):c.685G>A(p.Val229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,205,459 control chromosomes in the GnomAD database, including 2 homozygotes. There are 365 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004840.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF6 | NM_004840.3 | c.685G>A | p.Val229Ile | missense_variant | 6/22 | ENST00000250617.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF6 | ENST00000250617.7 | c.685G>A | p.Val229Ile | missense_variant | 6/22 | 1 | NM_004840.3 | P1 | |
ARHGEF6 | ENST00000370622.5 | c.223G>A | p.Val75Ile | missense_variant | 5/21 | 1 | |||
ARHGEF6 | ENST00000370620.5 | c.223G>A | p.Val75Ile | missense_variant | 5/21 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 164AN: 111617Hom.: 2 Cov.: 23 AF XY: 0.00133 AC XY: 45AN XY: 33817
GnomAD3 exomes AF: 0.000784 AC: 140AN: 178667Hom.: 0 AF XY: 0.000471 AC XY: 30AN XY: 63657
GnomAD4 exome AF: 0.000995 AC: 1088AN: 1093790Hom.: 0 Cov.: 28 AF XY: 0.000890 AC XY: 320AN XY: 359524
GnomAD4 genome ? AF: 0.00147 AC: 164AN: 111669Hom.: 2 Cov.: 23 AF XY: 0.00133 AC XY: 45AN XY: 33879
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 30, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 20, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 01, 2014 | The p.V229I variant (also known as c.685G>A), located in coding exon 6 of the ARHGEF6 gene, results from a G to A substitution at nucleotide position 685. The valine at codon 229 is replaced by isoleucine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs75329154. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0% (0/503) total male alleles studied.. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.08% (2/2443) total male alleles studied, having been observed in 0.18% (1/571) African American male alleles and 0.05% (1/1872) European American male alleles. This amino acid position is not conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
ARHGEF6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Non-syndromic X-linked intellectual disability Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at