chr17-82082645-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004104.5(FASN):c.5801G>A(p.Arg1934His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,610,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. R1934C) 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.5801G>A | p.Arg1934His | missense_variant | 34/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.5801G>A | p.Arg1934His | missense_variant | 34/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.5801G>A | p.Arg1934His | missense_variant | 34/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.5795G>A | p.Arg1932His | missense_variant | 34/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000106 AC: 26AN: 244844Hom.: 0 AF XY: 0.000120 AC XY: 16AN XY: 133878
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1458082Hom.: 0 Cov.: 38 AF XY: 0.0000372 AC XY: 27AN XY: 725570
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74354
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1934 of the FASN protein (p.Arg1934His). This variant is present in population databases (rs200897153, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. 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: 462082). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine 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