NM_002004.4:c.47C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002004.4(FDPS):c.47C>T(p.Pro16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,578,498 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

FDPS
NM_002004.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Publications

2 publications found

Variant links:

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

FDPS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087370336).

BS2

High AC in GnomAd4 at 23 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDPS	NM_002004.4	MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 2 of 11	NP_001995.1	P14324-1
FDPS	NM_001135821.2		c.47C>T	p.Pro16Leu	missense	Exon 2 of 11	NP_001129293.1	P14324-1
FDPS	NM_001135822.2		c.-1-228C>T		intron	N/A	NP_001129294.1	P14324-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDPS	ENST00000368356.9	TSL:2 MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 2 of 11	ENSP00000357340.4	P14324-1
FDPS	ENST00000356657.10	TSL:1	c.47C>T	p.Pro16Leu	missense	Exon 2 of 11	ENSP00000349078.6	P14324-1
FDPS	ENST00000851541.1		c.47C>T	p.Pro16Leu	missense	Exon 2 of 11	ENSP00000521600.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000167

AC:

AN:

210026

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000296

AC:

422

AN:

1426392

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

201

AN XY:

704514

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

32950

American (AMR)

AF:

0.0000246

AC:

AN:

40590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25076

East Asian (EAS)

AF:

0.00

AC:

AN:

38600

South Asian (SAS)

AF:

0.000423

AC:

AN:

82646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51700

Middle Eastern (MID)

AF:

0.000386

AC:

AN:

5178

European-Non Finnish (NFE)

AF:

0.000336

AC:

366

AN:

1090826

Other (OTH)

AF:

0.000289

AC:

AN:

58826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000368

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000140

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.83

M_CAP

Benign

0.021

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PhyloP100

1.5

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.48

REVEL

Benign

0.21

Sift

Benign

0.10

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.40

MVP

0.43

MPC

0.30

ClinPred

0.080

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.20

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over