rs1469173192
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004104.5(FASN):c.1018G>T(p.Ala340Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,423,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.1018G>T | p.Ala340Ser | missense_variant | Exon 8 of 43 | 1 | NM_004104.5 | ENSP00000304592.2 | ||
FASN | ENST00000634990.1 | c.1018G>T | p.Ala340Ser | missense_variant | Exon 8 of 43 | 5 | ENSP00000488964.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000211 AC: 3AN: 1423690Hom.: 0 Cov.: 37 AF XY: 0.00000284 AC XY: 2AN XY: 705274
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
This sequence change replaces alanine with serine at codon 340 of the FASN protein (p.Ala340Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FASN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on FASN function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at