Variant 8-11808810-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000220584.9(FDFT1):c.116G>C(p.Ser39Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

FDFT1
ENST00000220584.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15599957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDFT1	NM_004462.5 linkuse as main transcript	c.116G>C	p.Ser39Thr	missense_variant	2/8	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9 linkuse as main transcript	c.116G>C	p.Ser39Thr	missense_variant	2/8	1	NM_004462.5	ENSP00000220584	P1	P37268-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250974

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135668

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.116G>C (p.S39T) alteration is located in exon 2 (coding exon 2) of the FDFT1 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.26

T;T;T;T;.;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

.;.;T;.;T;T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.1

L;L;.;L;L;.;.

MutationTaster

Benign

0.84

D;D;D;D;D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.32

.;.;N;N;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.37

.;.;T;T;T;T;.

Sift4G

Benign

0.54

T;T;T;T;T;T;.

Polyphen

0.0010

B;B;.;B;.;B;.

Vest4

0.22

MutPred

0.28

Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);Loss of disorder (P = 0.0648);.;.;

MVP

0.47

ClinPred

0.18

GERP RS

4.7

Varity_R

0.36

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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