Genetic Variant FDFT1:c.100-86_100-85insCTCCCA (chr8-11808704-C-CCCCACT) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_001287750.2(FDFT1):c.191_192insCTCCCA(p.Pro63_Gln64insHisSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000604 in 1,323,470 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000060 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FDFT1
NM_001287750.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.143

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001287750.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5 link	c.100-86_100-85insCTCCCA		intron_variant	Intron 1 of 7	ENST00000220584.9	NP_004453.3	P37268-1Q6IAX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9 link	c.100-86_100-85insCTCCCA		intron_variant	Intron 1 of 7	1	NM_004462.5	ENSP00000220584.4		P37268-1

Frequencies

GnomAD3 genomes

AF:

0.0000121

AC:

AN:

82626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000604

AC:

AN:

1323470

Hom.:

Cov.:

AF XY:

0.00000460

AC XY:

AN XY:

651776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

31308

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

29454

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

22142

Gnomad4 EAS exome

AF:

0.000113

AC:

AN:

35458

Gnomad4 SAS exome

AF:

0.0000270

AC:

AN:

73994

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

40698

Gnomad4 NFE exome

AF:

9.70e-7

AC:

AN:

1030612

Gnomad4 Remaining exome

AF:

0.0000182

AC:

AN:

54800

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000121

AC:

AN:

82626

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

39380

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000395

AC:

0.000394945

AN:

0.000394945

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FDFT1: PM2, BP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=95/5

polymorphism

Splicing

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