Genetic Variant IDI1:p.Ala8Glu (chr10-1048981-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004508.4(IDI1):c.23C>A(p.Ala8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,377,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 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. A8G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

IDI1
NM_004508.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.686

Publications

0 publications found

Variant links:

Genes affected

IDI1 (HGNC:5387): (isopentenyl-diphosphate delta isomerase 1) IDI1 encodes a peroxisomally-localized enzyme that catalyzes the interconversion of isopentenyl diphosphate (IPP) to its highly electrophilic isomer, dimethylallyl diphosphate (DMAPP), which are the substrates for the successive reaction that results in the synthesis of farnesyl diphosphate and, ultimately, cholesterol. It has been shown in peroxisomal deficiency diseases such as Zellweger syndrome and neonatal adrenoleukodystrophy that there is reduction in IPP isomerase activity. [provided by RefSeq, Jul 2008]

IDI1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08941692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004508.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDI1	NM_004508.4	MANE Select	c.23C>A	p.Ala8Glu	missense	Exon 1 of 5	NP_004499.2
IDI1	NM_001317955.2		c.-28-4810C>A		intron	N/A	NP_001304884.1	A0A8Q3WKR8
IDI1	NR_134301.1		n.386C>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDI1	ENST00000381344.8	TSL:1 MANE Select	c.23C>A	p.Ala8Glu	missense	Exon 1 of 5	ENSP00000370748.3	Q13907-2
IDI1	ENST00000491735.1	TSL:1	n.123C>A		non_coding_transcript_exon	Exon 1 of 4
IDI1	ENST00000695775.1		c.-146C>A		upstream_gene	N/A	ENSP00000512165.1	A0A8Q3WKR8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1377546

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

680216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29446

American (AMR)

AF:

0.00

AC:

AN:

34466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23872

East Asian (EAS)

AF:

0.00

AC:

AN:

34736

South Asian (SAS)

AF:

0.00

AC:

AN:

78046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.0000353

AC:

AN:

1075756

Other (OTH)

AF:

0.0000349

AC:

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.8

(source)

DANN

Benign

0.89

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.35

M_CAP

Benign

0.011

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

PhyloP100

-0.69

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.53

REVEL

Benign

0.010

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.047

Polyphen

0.25

Vest4

0.25

MutPred

0.40

Loss of methylation at R3 (P = 0.0413)

MVP

0.25

MPC

0.67

ClinPred

0.70

GERP RS

-0.23

PromoterAI

-0.057

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.29

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over