14-95133360-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BS2

The NM_177438.3(DICER1):​c.99A>T​(p.Gln33His) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q33Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DICER1
NM_177438.3 missense

Scores

2
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.65

Publications

0 publications found
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]
DICER1 Gene-Disease associations (from GenCC):
  • DICER1-related tumor predisposition
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • pleuropulmonary blastoma
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • DICER1 syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS2
High AC in GnomAdExome4 at 5 AD,Unknown gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DICER1NM_177438.3 linkc.99A>T p.Gln33His missense_variant Exon 2 of 27 ENST00000343455.8 NP_803187.1 Q9UPY3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DICER1ENST00000343455.8 linkc.99A>T p.Gln33His missense_variant Exon 2 of 27 1 NM_177438.3 ENSP00000343745.3 Q9UPY3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000402
AC:
1
AN:
249006
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727218
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.0000936
AC:
5
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111998
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;T;T;T;.;T;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.92
.;.;D;.;D;.;D
M_CAP
Benign
0.068
D
MetaRNN
Uncertain
0.43
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.076
T
MutationAssessor
Benign
0.55
N;N;N;N;N;.;.
PhyloP100
4.6
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.96
N;N;N;N;N;N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0030
D;D;D;D;D;D;D
Sift4G
Benign
0.16
T;T;T;T;T;.;.
Polyphen
1.0
D;D;D;D;.;.;.
Vest4
0.82
MutPred
0.47
Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.85
MPC
1.4
ClinPred
0.64
D
GERP RS
5.6
PromoterAI
0.025
Neutral
Varity_R
0.46
gMVP
0.75
Mutation Taster
=53/47
polymorphism

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

Other links and lift over

dbSNP: rs773456851; hg19: chr14-95599697; API