rs562846615
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004104.5(FASN):c.820C>T(p.Arg274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,605,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.820C>T | p.Arg274Cys | missense_variant | 7/43 | ENST00000306749.4 | NP_004095.4 | |
FASN | XM_011523538.3 | c.820C>T | p.Arg274Cys | missense_variant | 7/43 | XP_011521840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.820C>T | p.Arg274Cys | missense_variant | 7/43 | 1 | NM_004104.5 | ENSP00000304592.2 | ||
FASN | ENST00000634990.1 | c.820C>T | p.Arg274Cys | missense_variant | 7/43 | 5 | ENSP00000488964.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000467 AC: 11AN: 235568Hom.: 0 AF XY: 0.0000468 AC XY: 6AN XY: 128154
GnomAD4 exome AF: 0.0000337 AC: 49AN: 1453252Hom.: 0 Cov.: 36 AF XY: 0.0000401 AC XY: 29AN XY: 722388
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74434
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2023 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 531031). This variant has not been reported in the literature in individuals affected with FASN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 274 of the FASN protein (p.Arg274Cys). - |
FASN-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2024 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at