chr14-104780125-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PM2PP2BP4_StrongBP6BS1
The NM_001382430.1(AKT1):c.138C>A(p.Asp46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,688 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D46D) has been classified as Likely benign.
Frequency
Consequence
NM_001382430.1 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 |
---|---|---|---|---|---|---|---|
AKT1 | NM_001382430.1 | c.138C>A | p.Asp46Glu | missense_variant | 4/15 | ENST00000649815.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKT1 | ENST00000649815.2 | c.138C>A | p.Asp46Glu | missense_variant | 4/15 | NM_001382430.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 152216Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000327 AC: 82AN: 250802Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135762
GnomAD4 exome AF: 0.000500 AC: 730AN: 1461354Hom.: 0 Cov.: 31 AF XY: 0.000476 AC XY: 346AN XY: 727012
GnomAD4 genome ? AF: 0.000433 AC: 66AN: 152334Hom.: 1 Cov.: 33 AF XY: 0.000456 AC XY: 34AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with familial hypercholesterolemia (Marmontel et al., 2020); This variant is associated with the following publications: (PMID: 33111339, 33916788) - |
Cowden syndrome 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Hereditary cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | Jan 23, 2024 | - - |
AKT1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 07, 2022 | 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). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at