17-82089324-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004104.5(FASN):c.2026C>T(p.Arg676Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R676G) has been classified 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.2026C>T | p.Arg676Trp | missense_variant | 13/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.2026C>T | p.Arg676Trp | missense_variant | 13/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.2026C>T | p.Arg676Trp | missense_variant | 13/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.2026C>T | p.Arg676Trp | missense_variant | 13/43 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249866Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135624
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460560Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 726576
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2021 | The c.2026C>T (p.R676W) alteration is located in exon 13 (coding exon 12) of the FASN gene. This alteration results from a C to T substitution at nucleotide position 2026, causing the arginine (R) at amino acid position 676 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces arginine with tryptophan at codon 676 of the FASN protein (p.Arg676Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs759454700, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with FASN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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