rs863225241
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5
The NM_002004.4(FDPS):c.536G>A(p.Arg179Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
FDPS
NM_002004.4 missense
NM_002004.4 missense
Scores
7
6
2
Clinical Significance
Conservation
PhyloP100: 7.45
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity FPPS_HUMAN
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.987
PP5
?
Variant 1-155317996-G-A is Pathogenic according to our data. Variant chr1-155317996-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 217746.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FDPS | NM_002004.4 | c.536G>A | p.Arg179Gln | missense_variant | 5/11 | ENST00000368356.9 | |
RUSC1-AS1 | NR_145424.1 | n.637C>T | non_coding_transcript_exon_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FDPS | ENST00000368356.9 | c.536G>A | p.Arg179Gln | missense_variant | 5/11 | 2 | NM_002004.4 | ||
RUSC1-AS1 | ENST00000443642.1 | n.629C>T | non_coding_transcript_exon_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461518Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727060
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Porokeratosis 9, multiple types Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 23, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;.;D;.;T;D;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;.;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
T;T;D;T;D;D;T
Polyphen
1.0
.;.;D;.;.;D;.
Vest4
MutPred
0.97
.;.;Loss of phosphorylation at T177 (P = 0.2009);.;Loss of phosphorylation at T177 (P = 0.2009);Loss of phosphorylation at T177 (P = 0.2009);.;
MVP
MPC
0.68
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at