chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCAC

Position:

• chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCAC

Variant summary

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

The NM_004462.5(FDFT1):​c.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC variant causes a intron 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_004462.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.258

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-46_100-45insCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCCCACTCC		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 4 AN: 148922 Hom.: 0 Cov.: 0

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: 29 AN: 1366052 Hom.: 3 Cov.: 0 AF XY: 0.0000387 AC XY: 26 AN XY: 672638

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: 4 AN: 149034 Hom.: 0 Cov.: 0 AF XY: 0.0000275 AC XY: 2 AN XY: 72636

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

Submissions by phenotype

FDFT1-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 21, 2023

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71711801; hg19: chr8-11666218;