Genetic Variant FDFT1:c.100-86_100-85insCTCCCA (chr8-11808704-C-CCCCACT) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_001287750.2(FDFT1):c.191_192insCTCCCA(p.Pro63_Gln64insHisSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000604 in 1,323,470 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000060 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

FDFT1
NM_001287750.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.143

Publications

0 publications found

Variant links:

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

FDFT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001287750.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287750.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDFT1	NM_004462.5	MANE Select	c.100-86_100-85insCTCCCA		intron	N/A	NP_004453.3
FDFT1	NM_001287750.2		c.191_192insCTCCCA	p.Pro63_Gln64insHisSer	disruptive_inframe_insertion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
FDFT1	NM_001287742.2		c.100-86_100-85insCTCCCA		intron	N/A	NP_001274671.1	Q6IAX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.100-86_100-85insCTCCCA		intron	N/A	ENSP00000220584.4	P37268-1
FDFT1	ENST00000529464.5	TSL:1	n.100-959_100-958insCTCCCA		intron	N/A	ENSP00000434770.1	E9PNJ2
FDFT1	ENST00000525954.5	TSL:2	c.191_192insCTCCCA	p.Pro63_Gln64insHisSer	disruptive_inframe_insertion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

Frequencies

GnomAD3 genomes

AF:

0.0000121

AC:

AN:

82626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000604

AC:

AN:

1323470

Hom.:

Cov.:

AF XY:

0.00000460

AC XY:

AN XY:

651776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31308

American (AMR)

AF:

0.00

AC:

AN:

29454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22142

East Asian (EAS)

AF:

0.000113

AC:

AN:

35458

South Asian (SAS)

AF:

0.0000270

AC:

AN:

73994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5004

European-Non Finnish (NFE)

AF:

9.70e-7

AC:

AN:

1030612

Other (OTH)

AF:

0.0000182

AC:

AN:

54800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000121

AC:

AN:

82626

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

39380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23610

American (AMR)

AF:

0.00

AC:

AN:

7336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2118

East Asian (EAS)

AF:

0.000395

AC:

AN:

2532

South Asian (SAS)

AF:

0.00

AC:

AN:

1784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39068

Other (OTH)

AF:

0.00

AC:

AN:

1010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=95/5

polymorphism

(source)

Splicing

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

Publications

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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