Variant chr8-11808823-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004462.5(FDFT1):c.129C>G(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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

FDFT1
NM_004462.5 missense

Scores

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]

FDFT1 links:

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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 linkuse as main transcript	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 linkuse as main transcript	c.129C>G	p.Cys43Trp	missense_variant	2/8	1	NM_004462.5	P1	P37268-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251086

Hom.:

AF XY:

0.00000737

AC XY:

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:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

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.:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

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

LIST_S2

Uncertain

0.95

.;.;D;.;D;D;D

M_CAP

Pathogenic

0.85

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.096

MutationAssessor

Uncertain

2.4

M;M;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.78

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over