8-11808823-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004462.5(FDFT1):āc.129C>Gā(p.Cys43Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
FDFT1
NM_004462.5 missense
NM_004462.5 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 1.35
Genes affected
FDFT1 (HGNC:3629): (farnesyl-diphosphate farnesyltransferase 1) This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FDFT1 | NM_004462.5 | c.129C>G | p.Cys43Trp | missense_variant | 2/8 | ENST00000220584.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FDFT1 | ENST00000220584.9 | c.129C>G | p.Cys43Trp | missense_variant | 2/8 | 1 | NM_004462.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251086Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135716
GnomAD3 exomes
AF:
AC:
2
AN:
251086
Hom.:
AF XY:
AC XY:
1
AN XY:
135716
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461690Hom.: 0 Cov.: 44 AF XY: 0.00000550 AC XY: 4AN XY: 727116
GnomAD4 exome
AF:
AC:
7
AN:
1461690
Hom.:
Cov.:
44
AF XY:
AC XY:
4
AN XY:
727116
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | FDFT1: PM2, PP3 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.;M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
.;.;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;.
Polyphen
D;D;.;D;.;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0098);Gain of MoRF binding (P = 0.0098);Gain of MoRF binding (P = 0.0098);Gain of MoRF binding (P = 0.0098);Gain of MoRF binding (P = 0.0098);.;.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at