chr19-33301415-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_004364.5(CEBPA):c.1000G>A(p.Glu334Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,300 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E334Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.1000G>A | p.Glu334Lys | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.1105G>A | p.Glu369Lys | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.958G>A | p.Glu320Lys | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.643G>A | p.Glu215Lys | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.1000G>A | p.Glu334Lys | missense_variant | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.137C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246288Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134092
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459300Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726098
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Acute myeloid leukemia Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | clinical testing | Department of Zoology, Division of Science and Technology, University of Education | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 580178). This variant has not been reported in the literature in individuals affected with CEBPA-related conditions. This variant is present in population databases (rs369632687, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 334 of the CEBPA protein (p.Glu334Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at