rs779530679
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_177438.3(DICER1):āc.3379A>Gā(p.Ile1127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,030 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1127S) has been classified as Uncertain significance.
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.3379A>G | p.Ile1127Val | missense_variant | 21/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.3379A>G | p.Ile1127Val | missense_variant | 21/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250810Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135674
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727232
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1127 of the DICER1 protein (p.Ile1127Val). This variant is present in population databases (rs779530679, gnomAD 0.0009%). 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: 477138). 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 | Aug 09, 2022 | The p.I1127V variant (also known as c.3379A>G), located in coding exon 20 of the DICER1 gene, results from an A to G substitution at nucleotide position 3379. The isoleucine at codon 1127 is replaced by valine, an amino acid with highly 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