rs372065783
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004104.5(FASN):c.6553C>T(p.Arg2185Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000289 in 1,594,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R2185Q) has been classified as Benign.
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.6553C>T | p.Arg2185Trp | missense_variant | 38/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.6553C>T | p.Arg2185Trp | missense_variant | 38/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.6553C>T | p.Arg2185Trp | missense_variant | 38/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.6547C>T | p.Arg2183Trp | missense_variant | 38/43 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 6AN: 215828Hom.: 0 AF XY: 0.0000427 AC XY: 5AN XY: 117114
GnomAD4 exome AF: 0.0000291 AC: 42AN: 1441992Hom.: 0 Cov.: 36 AF XY: 0.0000293 AC XY: 21AN XY: 715540
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.6553C>T (p.R2185W) alteration is located in exon 38 (coding exon 37) of the FASN gene. This alteration results from a C to T substitution at nucleotide position 6553, causing the arginine (R) at amino acid position 2185 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 | Jul 25, 2023 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2185 of the FASN protein (p.Arg2185Trp). This variant has not been reported in the literature in individuals affected with FASN-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 565692). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at