X-63706288-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001353921.2(ARHGEF9):c.372C>T(p.His124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000957 in 1,202,155 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001353921.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF9 | NM_001353921.2 | c.372C>T | p.His124= | synonymous_variant | 3/10 | ENST00000671741.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF9 | ENST00000671741.2 | c.372C>T | p.His124= | synonymous_variant | 3/10 | NM_001353921.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000452 AC: 5AN: 110653Hom.: 0 Cov.: 22 AF XY: 0.0000609 AC XY: 2AN XY: 32839
GnomAD3 exomes AF: 0.0000417 AC: 7AN: 167825Hom.: 0 AF XY: 0.0000364 AC XY: 2AN XY: 54883
GnomAD4 exome AF: 0.000101 AC: 110AN: 1091502Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 32AN XY: 358052
GnomAD4 genome AF: 0.0000452 AC: 5AN: 110653Hom.: 0 Cov.: 22 AF XY: 0.0000609 AC XY: 2AN XY: 32839
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 28, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2018 | 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Developmental and epileptic encephalopathy, 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at