rs780441119
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004104.5(FASN):āc.1213A>Gā(p.Arg405Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,604,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. R405R) has been classified as Likely benign.
Frequency
Consequence
NM_004104.5 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 |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.1213A>G | p.Arg405Gly | missense_variant | 9/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.1213A>G | p.Arg405Gly | missense_variant | 9/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.1213A>G | p.Arg405Gly | missense_variant | 9/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.1213A>G | p.Arg405Gly | missense_variant | 9/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000263 AC: 6AN: 228020Hom.: 0 AF XY: 0.0000321 AC XY: 4AN XY: 124456
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1452862Hom.: 0 Cov.: 35 AF XY: 0.0000166 AC XY: 12AN XY: 722236
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74278
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FASN-related disease. This variant is present in population databases (rs780441119, ExAC 0.01%). This sequence change replaces arginine with glycine at codon 405 of the FASN protein (p.Arg405Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at