rs369189695
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_177438.3(DICER1):āc.739A>Gā(p.Thr247Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.739A>G | p.Thr247Ala | missense_variant | 7/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.739A>G | p.Thr247Ala | missense_variant | 7/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000134 AC: 2AN: 149168Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251248Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135790
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1455002Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 724316
GnomAD4 genome AF: 0.0000134 AC: 2AN: 149168Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 1AN XY: 72436
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 247 of the DICER1 protein (p.Thr247Ala). This variant is present in population databases (rs369189695, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 477283). 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 DICER1 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2024 | The p.T247A variant (also known as c.739A>G), located in coding exon 6 of the DICER1 gene, results from an A to G substitution at nucleotide position 739. The threonine at codon 247 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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