NM_004969.4:c.1740-197_1740-190dupACACACAC

Variant names:

• chr10-92479610-A-AGTGTGTGT
• rs3831274
• NM_004969.4:c.1740-197_1740-190dupACACACAC

Variant summary

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

The NM_004969.4(IDE):​c.1740-197_1740-190dupACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IDE NM_004969.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 1 publications found

Genes affected

IDE (HGNC:5381): (insulin degrading enzyme) This gene encodes a zinc metallopeptidase that degrades intracellular insulin, and thereby terminates insulins activity, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. The preferential affinity of this enzyme for insulin results in insulin-mediated inhibition of the degradation of other peptides such as beta-amyloid. Deficiencies in this protein's function are associated with Alzheimer's disease and type 2 diabetes mellitus but mutations in this gene have not been shown to be causitive for these diseases. This protein localizes primarily to the cytoplasm but in some cell types localizes to the extracellular space, cell membrane, peroxisome, and mitochondrion. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but have not been experimentally verified.[provided by RefSeq, Sep 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	NM_004969.4	MANE Select	c.1740-197_1740-190dupACACACAC		intron	N/A	NP_004960.2	P14735-1
	IDE	NM_001322793.2		c.1740-829_1740-822dupACACACAC		intron	N/A	NP_001309722.1	A0A3B3ISG5
	IDE	NM_001322794.2		c.1623-197_1623-190dupACACACAC		intron	N/A	NP_001309723.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDE	ENST00000265986.11	TSL:1 MANE Select	c.1740-197_1740-190dupACACACAC		intron	N/A	ENSP00000265986.6	P14735-1
	IDE	ENST00000478361.6	TSL:1	n.*2074-197_*2074-190dupACACACAC		intron	N/A	ENSP00000473506.1	R4GN65
	IDE	ENST00000971392.1		c.1740-197_1740-190dupACACACAC		intron	N/A	ENSP00000641451.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 320100 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 167342

African (AFR) AF: 0.00 AC: 0 AN: 9968

American (AMR) AF: 0.00 AC: 0 AN: 14358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10208

East Asian (EAS) AF: 0.00 AC: 0 AN: 22536

South Asian (SAS) AF: 0.00 AC: 0 AN: 26638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1418

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 194106

Other (OTH) AF: 0.00 AC: 0 AN: 19126

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3831274; hg19: chr10-94239367;