rs387907012
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_016097.5(IER3IP1):āc.233T>Cā(p.Leu78Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,563,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L78L) has been classified as Likely benign.
Frequency
Consequence
NM_016097.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IER3IP1 | NM_016097.5 | c.233T>C | p.Leu78Pro | missense_variant | 3/3 | ENST00000256433.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IER3IP1 | ENST00000256433.6 | c.233T>C | p.Leu78Pro | missense_variant | 3/3 | 1 | NM_016097.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1411584Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 704874
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
Microcephaly, epilepsy, and diabetes syndrome 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2012 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 23, 2021 | - - |
Microcephaly, epilepsy, and diabetes syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 07, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 30786). This missense change has been observed in individuals with primary microcephaly, epilepsy, neonatal diabetes (PMID: 21835305, 22991235, 23771172, 28711742). It has also been observed to segregate with disease in related individuals. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 78 of the IER3IP1 protein (p.Leu78Pro). This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at