rs376650647
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004104.5(FASN):c.2984G>A(p.Arg995His) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,612,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R995C) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.2984G>A | p.Arg995His | missense_variant | 19/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.2984G>A | p.Arg995His | missense_variant | 19/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.2984G>A | p.Arg995His | missense_variant | 19/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.2984G>A | p.Arg995His | missense_variant | 19/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 248982Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135286
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460194Hom.: 0 Cov.: 35 AF XY: 0.00000964 AC XY: 7AN XY: 726360
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 531055). This variant has not been reported in the literature in individuals affected with FASN-related conditions. This variant is present in population databases (rs376650647, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 995 of the FASN protein (p.Arg995His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at