rs587778192
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4
The NM_004364.5(CEBPA):c.1009A>T(p.Thr337Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000133 in 1,611,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. T337M) has been classified as Uncertain significance.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.1009A>T | p.Thr337Ser | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.1114A>T | p.Thr372Ser | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.967A>T | p.Thr323Ser | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.652A>T | p.Thr218Ser | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.1009A>T | p.Thr337Ser | missense_variant | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.128T>A | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245796Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133920
GnomAD4 exome AF: 0.000144 AC: 210AN: 1458878Hom.: 0 Cov.: 31 AF XY: 0.000132 AC XY: 96AN XY: 725872
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 337 of the CEBPA protein (p.Thr337Ser). This variant is present in population databases (rs587778192, gnomAD 0.005%). This missense change has been observed in individual(s) with acute myeloid leukemia, but the germline nature of this variant is unclear (PMID: 28250006). ClinVar contains an entry for this variant (Variation ID: 133885). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEBPA protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 26, 2023 | - - |
not specified Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 03, 2022 | DNA sequence analysis of the CEBPA gene demonstrated a sequence change, c.1009A>T, in exon 1 that results in an amino acid change, p.Thr337Ser. This sequence change has been described in the gnomAD database with a frequency of 0.005% in the non-Finnish European subpopulation (dbSNP rs587778192). The p.Thr337Ser change affects a highly conserved amino acid residue located in a domain of the CEBPA protein that is known to be functional. The p.Thr337Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with CEBPA-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr337Ser change remains unknown at this time. - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 01, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31751678, 24728327, 28250006, 21455213) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at