chr10-1044101-C-A

Variant names:

• chr10-1044101-C-A
• rs1048256396
• NM_004508.4:c.211G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004508.4(IDI1):​c.211G>T​(p.Val71Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IDI1 NM_004508.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40

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]

IDI2-AS1 (HGNC:30885): (IDI2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDI1	NM_004508.4	c.211G>T	p.Val71Phe	missense_variant	Exon 2 of 5	ENST00000381344.8	NP_004499.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDI1	ENST00000381344.8	c.211G>T	p.Val71Phe	missense_variant	Exon 2 of 5	1	NM_004508.4	ENSP00000370748.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461528 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.25
Sift	Benign	0.032	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		0.99	.;D
Vest4		0.39
MutPred		0.37		.;Gain of catalytic residue at V71 (P = 0.0388);
MVP		0.59
MPC		1.4
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.53
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs1048256396; hg19: chr10-1090041;