rs756441396
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The ENST00000306749.4(FASN):c.1118G>A(p.Arg373Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,590,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R373R) has been classified as Likely benign.
Frequency
Consequence
ENST00000306749.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.1118G>A | p.Arg373Gln | missense_variant | 9/43 | ENST00000306749.4 | NP_004095.4 | |
FASN | XM_011523538.3 | c.1118G>A | p.Arg373Gln | missense_variant | 9/43 | XP_011521840.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.1118G>A | p.Arg373Gln | missense_variant | 9/43 | 1 | NM_004104.5 | ENSP00000304592 | P1 | |
FASN | ENST00000634990.1 | c.1118G>A | p.Arg373Gln | missense_variant | 9/43 | 5 | ENSP00000488964 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000245 AC: 5AN: 204190Hom.: 0 AF XY: 0.0000452 AC XY: 5AN XY: 110672
GnomAD4 exome AF: 0.0000153 AC: 22AN: 1437978Hom.: 1 Cov.: 35 AF XY: 0.0000210 AC XY: 15AN XY: 713032
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2022 | The c.1118G>A (p.R373Q) alteration is located in exon 9 (coding exon 8) of the FASN gene. This alteration results from a G to A substitution at nucleotide position 1118, causing the arginine (R) at amino acid position 373 to be replaced by a glutamine (Q). 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 | Labcorp Genetics (formerly Invitae), Labcorp | Mar 13, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 373 of the FASN protein (p.Arg373Gln). This variant is present in population databases (rs756441396, gnomAD 0.009%). 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: 574406). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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