rs925971986
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004104.5(FASN):āc.5527A>Gā(p.Met1843Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,622 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
FASN
NM_004104.5 missense
NM_004104.5 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.5527A>G | p.Met1843Val | missense_variant | 32/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.5527A>G | p.Met1843Val | missense_variant | 32/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.5527A>G | p.Met1843Val | missense_variant | 32/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.5521A>G | p.Met1841Val | missense_variant | 32/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249996Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135626
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460464Hom.: 0 Cov.: 36 AF XY: 0.0000110 AC XY: 8AN XY: 726542
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This variant has not been reported in the literature in individuals affected with FASN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1843 of the FASN protein (p.Met1843Val). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 580742). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Uncertain
T;T
Polyphen
D;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at