rs755007541
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_177438.3(DICER1):āc.1017G>Cā(p.Glu339Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.1017G>C | p.Glu339Asp | missense_variant | 8/27 | ENST00000343455.8 | NP_803187.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.1017G>C | p.Glu339Asp | missense_variant | 8/27 | 1 | NM_177438.3 | ENSP00000343745.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249106Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134944
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461556Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727060
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 28, 2017 | This sequence change replaces glutamic acid with aspartic acid at codon 339 of the DICER1 protein (p.Glu339Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs755007541, ExAC 0.01%). This variant has not been reported in the literature in individuals with DICER1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 03, 2022 | The p.E339D variant (also known as c.1017G>C), located in coding exon 7 of the DICER1 gene, results from a G to C substitution at nucleotide position 1017. The glutamic acid at codon 339 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at