rs112444332
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004104.5(FASN):c.3133G>A(p.Gly1045Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,612,668 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 (★).
Frequency
Consequence
NM_004104.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.3133G>A | p.Gly1045Ser | missense_variant | 20/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.3133G>A | p.Gly1045Ser | missense_variant | 20/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.3133G>A | p.Gly1045Ser | missense_variant | 20/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.3133G>A | p.Gly1045Ser | missense_variant | 20/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000520 AC: 13AN: 249954Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135588
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1460380Hom.: 0 Cov.: 36 AF XY: 0.0000358 AC XY: 26AN XY: 726506
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74456
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1045 of the FASN protein (p.Gly1045Ser). This variant is present in population databases (rs112444332, gnomAD 0.01%). 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: 573864). 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 serine 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