8-11802851-C-T

Variant names:

• chr8-11802851-C-T
• rs574662343
• NM_004462.5:c.19C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004462.5(FDFT1):​c.19C>T​(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FDFT1 NM_004462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.19C>T	p.Leu7Phe	missense_variant	Exon 1 of 8	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.19C>T	p.Leu7Phe	missense_variant	Exon 1 of 8	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.77	D;D;T;D;.;T
Eigen	Benign	0.068
Eigen_PC	Benign	-0.057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;.;D;.;D;D
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M;M;.;M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	.;.;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0070	.;.;D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D
Polyphen		1.0	D;D;.;D;.;D
Vest4		0.80
MutPred		0.55		Loss of catalytic residue at L7 (P = 0.0419);Loss of catalytic residue at L7 (P = 0.0419);Loss of catalytic residue at L7 (P = 0.0419);Loss of catalytic residue at L7 (P = 0.0419);Loss of catalytic residue at L7 (P = 0.0419);Loss of catalytic residue at L7 (P = 0.0419);
MVP		0.54
ClinPred		0.97	D
GERP RS		-0.38
Varity_R		0.38

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

Other links and lift over

dbSNP: rs574662343; hg19: chr8-11660360;