17-82083522-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004104.5(FASN):āc.5336C>Gā(p.Pro1779Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1779L) 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 -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.5336C>G | p.Pro1779Arg | missense_variant | 31/43 | 1 | NM_004104.5 | ENSP00000304592.2 | ||
FASN | ENST00000634990.1 | c.5330C>G | p.Pro1777Arg | missense_variant | 31/43 | 5 | ENSP00000488964.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249424Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135466
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460436Hom.: 0 Cov.: 37 AF XY: 0.00000826 AC XY: 6AN XY: 726514
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74392
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 06, 2024 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1779 of the FASN protein (p.Pro1779Arg). This variant is present in population databases (rs2229426, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with FASN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at