1-155309895-GTG-CTA

Variant names:

• chr1-155309895-GTG-CTA
• NM_002004.4:c.106_108delGTGinsCTA
• FDPS p.Val36Leu

Variant summary

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

The NM_002004.4(FDPS):​c.106_108delGTGinsCTA​(p.Val36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V36M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FDPS NM_002004.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

FDPS (HGNC:3631): (farnesyl diphosphate synthase) This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

FDPS Gene-Disease associations (from GenCC):

• porokeratosis 9, multiple types

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• disseminated superficial actinic porokeratosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002004.4. 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
	FDPS	NM_002004.4	MANE Select	c.106_108delGTGinsCTA	p.Val36Leu	missense	N/A	NP_001995.1	P14324-1
	FDPS	NM_001135821.2		c.106_108delGTGinsCTA	p.Val36Leu	missense	N/A	NP_001129293.1	P14324-1
	FDPS	NM_001135822.2		c.-1-169_-1-167delGTGinsCTA		intron	N/A	NP_001129294.1	P14324-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDPS	ENST00000368356.9	TSL:2 MANE Select	c.106_108delGTGinsCTA	p.Val36Leu	missense	N/A	ENSP00000357340.4	P14324-1
	FDPS	ENST00000356657.10	TSL:1	c.106_108delGTGinsCTA	p.Val36Leu	missense	N/A	ENSP00000349078.6	P14324-1
	FDPS	ENST00000851541.1		c.106_108delGTGinsCTA	p.Val36Leu	missense	N/A	ENSP00000521600.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-155279686;