rs1563290033

Variant names:

• chr8-11802585-TCTTCCTAGTGTGAGCG-T
• rs1563290033
• NM_001287742.2:c.-75+131_-75+146delCTTCCTAGTGTGAGCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The NM_001287742.2(FDFT1):​c.-75+131_-75+146delCTTCCTAGTGTGAGCG variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• squalene synthase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000255046 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• 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 VariationId is 587362.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	NM_001287742.2		c.-75+131_-75+146delCTTCCTAGTGTGAGCG		intron	N/A	NP_001274671.1	Q6IAX1
	FDFT1	NM_001287743.2		c.-74-173_-74-158delCTTCCTAGTGTGAGCG		intron	N/A	NP_001274672.1	P37268-1
	FDFT1	NM_001287744.2		c.-93-6208_-93-6193delCTTCCTAGTGTGAGCG		intron	N/A	NP_001274673.1	P37268-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000530337.6	TSL:3	c.-75+131_-75+146delCTTCCTAGTGTGAGCG		intron	N/A	ENSP00000431852.2	P37268-1
	FDFT1	ENST00000615631.5	TSL:5	c.-74-173_-74-158delCTTCCTAGTGTGAGCG		intron	N/A	ENSP00000481481.1	P37268-1
	FDFT1	ENST00000866105.1		c.-75+131_-75+146delCTTCCTAGTGTGAGCG		intron	N/A	ENSP00000536164.1

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

African (AFR) AF: 0.00 AC: 0 AN: 13902

American (AMR) AF: 0.00 AC: 0 AN: 30858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16352

East Asian (EAS) AF: 0.00 AC: 0 AN: 27766

South Asian (SAS) AF: 0.00 AC: 0 AN: 57722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3618

European-Non Finnish (NFE) AF: 0.00000740 AC: 2 AN: 270296

Other (OTH) AF: 0.00 AC: 0 AN: 26490

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Squalene synthase deficiency (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0
Mutation Taster		=37/63	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1563290033; hg19: chr8-11660094;