rs906299601
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_177438.3(DICER1):c.968G>T(p.Gly323Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G323E) has been classified as Uncertain significance.
Frequency
Consequence
NM_177438.3 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 |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.968G>T | p.Gly323Val | missense_variant | 8/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.968G>T | p.Gly323Val | missense_variant | 8/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247478Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134200
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461466Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726992
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pleuropulmonary blastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Feb 09, 2023 | The DICER1 c.968G>T (p.Gly323Val) missense change has a maximum subpopulation frequency of 0.0009980% in gnomAD non-cancer v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function and no splicing effects are predicted, but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with DICER1-associated tumors. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.? - |
DICER1-related tumor predisposition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 323 of the DICER1 protein (p.Gly323Val). This variant is present in population databases (no rsID available, 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: 477296). 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 | Jan 21, 2022 | The c.968G>T (p.G323V) alteration is located in exon 8 (coding exon 7) of the DICER1 gene. This alteration results from a G to T substitution at nucleotide position 968, causing the glycine (G) at amino acid position 323 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at