rs1421575793
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004104.5(FASN):āc.4343G>Cā(p.Cys1448Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 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. C1448C) has been classified as Benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.4343G>C | p.Cys1448Ser | missense_variant | 25/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.4343G>C | p.Cys1448Ser | missense_variant | 25/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.4343G>C | p.Cys1448Ser | missense_variant | 25/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.4337G>C | p.Cys1446Ser | missense_variant | 25/43 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246794Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134528
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460320Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1AN XY: 726438
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2019 | 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FASN-related disease. This sequence change replaces cysteine with serine at codon 1448 of the FASN protein (p.Cys1448Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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