8-11802585-TCTTCCTAGTGTGAGCG-T

Position:

• chr8-11802585-TCTTCCTAGTGTGAGCG-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001287742.2(FDFT1):​c.-75+131_-75+146del variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FDFT1 NM_001287742.2 intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 5.98

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-11802585-TCTTCCTAGTGTGAGCG-T is Pathogenic according to our data. Variant chr8-11802585-TCTTCCTAGTGTGAGCG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 587362.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_001287742.2	c.-75+131_-75+146del		intron_variant
FDFT1	NM_001287743.2	c.-74-173_-74-158del		intron_variant
FDFT1	NM_001287744.2	c.-93-6208_-93-6193del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000530337.6	c.-75+131_-75+146del		intron_variant		3		P1
FDFT1	ENST00000615631.4	c.-74-173_-74-158del		intron_variant		5		P1
FDFT1	ENST00000446331.6			upstream_gene_variant		2
	ENST00000533405.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000421 AC: 2 AN: 475182 Hom.: 0 AF XY: 0.00000777 AC XY: 2 AN XY: 257290

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000740

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Squalene synthase deficiency Pathogenic:2 Other:1

Likely pathogenic, criteria provided, single submitter	research	Kids Research, The Children's Hospital at Westmead	May 29, 2018	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 25, 2018	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

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: rs1563290033; hg19: chr8-11660094;