rs1555741962
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM1PM2PM5BP4_Moderate
The NM_004364.5(CEBPA):āc.955A>Gā(p.Ser319Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S319I) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004364.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEBPA | NM_004364.5 | c.955A>G | p.Ser319Gly | missense_variant | 1/1 | ENST00000498907.3 | |
CEBPA | NM_001287424.2 | c.1060A>G | p.Ser354Gly | missense_variant | 1/1 | ||
CEBPA | NM_001287435.2 | c.913A>G | p.Ser305Gly | missense_variant | 1/1 | ||
CEBPA | NM_001285829.2 | c.598A>G | p.Ser200Gly | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEBPA | ENST00000498907.3 | c.955A>G | p.Ser319Gly | missense_variant | 1/1 | NM_004364.5 | P1 | ||
ENST00000587312.1 | n.182T>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460934Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726822
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 31, 2019 | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CEBPA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with glycine at codon 319 of the CEBPA protein (p.Ser319Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at