18-47156242-G-GA

Variant names:

• chr18-47156239-AGAG-AG
• NM_016097.5:c.194-10_194-9delCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016097.5(IER3IP1):​c.194-10_194-9delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IER3IP1 NM_016097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

Genes affected

IER3IP1 (HGNC:18550): (immediate early response 3 interacting protein 1) This gene encodes a small protein that is localized to the endoplasmic reticulum (ER) and may play a role in the ER stress response by mediating cell differentiation and apoptosis. Transcription of this gene is regulated by tumor necrosis factor alpha and specificity protein 1 (Sp1). Mutations in this gene may play a role in microcephaly, epilepsy, and diabetes syndrome (MEDS), and a pseudogene of this gene is located on the long arm of chromosome 12. [provided by RefSeq, Dec 2011]

IER3IP1 Gene-Disease associations (from GenCC):

• microcephaly, epilepsy, and diabetes syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• primary microcephaly-epilepsy-permanent neonatal diabetes syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ENSG00000267228 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016097.5. 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
	IER3IP1	NM_016097.5	MANE Select	c.194-10_194-9delCT		intron	N/A	NP_057181.1	Q9Y5U9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER3IP1	ENST00000256433.6	TSL:1 MANE Select	c.194-10_194-9delCT		intron	N/A	ENSP00000256433.3	Q9Y5U9
	ENSG00000267228	ENST00000588705.1	TSL:2	n.194-10_194-9delCT		intron	N/A	ENSP00000465194.1
	IER3IP1	ENST00000932440.1		c.311-10_311-9delCT		intron	N/A	ENSP00000602499.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

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

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

Other links and lift over

hg19: chr18-44682610;