8-11808823-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004462.5(FDFT1):ā€‹c.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

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
Variant links:
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
FDFT1NM_004462.5 linkuse as main transcriptc.129C>G p.Cys43Trp missense_variant 2/8 ENST00000220584.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FDFT1ENST00000220584.9 linkuse as main transcriptc.129C>G p.Cys43Trp missense_variant 2/81 NM_004462.5 P1P37268-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251086
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135716
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461690
Hom.:
0
Cov.:
44
AF XY:
0.00000550
AC XY:
4
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023FDFT1: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.94
D;D;D;D;.;T;.
Eigen
Benign
-0.077
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.95
.;.;D;.;D;D;D
M_CAP
Pathogenic
0.85
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.096
T
MutationAssessor
Uncertain
2.4
M;M;.;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-10
.;.;D;D;D;D;.
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0020
.;.;D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;.
Polyphen
1.0
D;D;.;D;.;D;.
Vest4
0.92
MutPred
0.69
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
0.88
ClinPred
1.0
D
GERP RS
-2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.99
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765417792; hg19: chr8-11666332; API