Genetic Variant FDFT1:c.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC (chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCAC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_001287750.2(FDFT1):c.231_232insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC(p.Ser77_Cys78insHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000021 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

FDFT1
NM_001287750.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

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 Likely_benign. Variant got -1 ACMG points.

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.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC		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.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC		intron_variant	Intron 1 of 7	1	NM_004462.5	ENSP00000220584.4		P37268-1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148922

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:

0.00

Gnomad SAS

AF:

0.000859

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000212

AC:

AN:

1366052

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

672638

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:

0.000382

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149034

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72636

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000859

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FDFT1-related disorder

Uncertain:1

Jul 21, 2023

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The FDFT1 c.231_232insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC variant is predicted to result in an in-frame amino acid insertion (p.Ser77_Cys78insHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSerHisSer). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

8-11808709-GTCCCACTCCCACTCCCACTCCCACTCCCAC-GTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCAC

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