rs965289045

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000343455.8(DICER1):​c.3637C>T​(p.Pro1213Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1213A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DICER1
ENST00000343455.8 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.77
Variant links:
Genes affected
DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DICER1. . Gene score misZ 4.2261 (greater than the threshold 3.09). Trascript score misZ 6.1353 (greater than threshold 3.09). GenCC has associacion of gene with goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome, DICER1-related tumor predisposition, DICER1 syndrome, pleuropulmonary blastoma.
BP4
Computational evidence support a benign effect (MetaRNN=0.14589688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DICER1NM_177438.3 linkuse as main transcriptc.3637C>T p.Pro1213Ser missense_variant 21/27 ENST00000343455.8 NP_803187.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DICER1ENST00000343455.8 linkuse as main transcriptc.3637C>T p.Pro1213Ser missense_variant 21/271 NM_177438.3 ENSP00000343745 P1Q9UPY3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Uncertain
0.076
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;T;T;.;.
Eigen
Benign
-0.13
Eigen_PC
Benign
0.085
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.86
.;.;D;.;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.15
T;T;T;T;T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
1.4
L;L;L;L;.;L
MutationTaster
Benign
0.91
D;D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.11
N;N;N;N;N;N
REVEL
Benign
0.090
Sift
Benign
0.11
T;T;T;T;T;T
Sift4G
Benign
0.68
T;T;T;T;T;T
Polyphen
0.0010
B;B;B;B;.;.
Vest4
0.45
MutPred
0.22
Loss of glycosylation at T1214 (P = 0.0786);Loss of glycosylation at T1214 (P = 0.0786);Loss of glycosylation at T1214 (P = 0.0786);Loss of glycosylation at T1214 (P = 0.0786);.;Loss of glycosylation at T1214 (P = 0.0786);
MVP
0.82
MPC
0.50
ClinPred
0.37
T
GERP RS
5.4
Varity_R
0.048
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-95570096; API