chr17-82083523-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004104.5(FASN):āc.5335C>Gā(p.Pro1779Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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 -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.5335C>G | p.Pro1779Ala | missense_variant | 31/43 | 1 | NM_004104.5 | ENSP00000304592.2 | ||
FASN | ENST00000634990.1 | c.5329C>G | p.Pro1777Ala | missense_variant | 31/43 | 5 | ENSP00000488964.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249474Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135484
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460464Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2AN XY: 726528
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 31, 2024 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1779 of the FASN protein (p.Pro1779Ala). This variant is present in population databases (rs753834341, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FASN-related conditions. ClinVar contains an entry for this variant (Variation ID: 462067). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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