chr5-31424470-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001382508.1(DROSHA):c.3218A>C(p.Asp1073Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000044 in 1,592,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
DROSHA
NM_001382508.1 missense, splice_region
NM_001382508.1 missense, splice_region
Scores
1
8
9
Splicing: ADA: 0.8254
1
1
Clinical Significance
Conservation
PhyloP100: 5.01
Genes affected
DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DROSHA
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DROSHA | NM_001382508.1 | c.3218A>C | p.Asp1073Ala | missense_variant, splice_region_variant | 28/36 | ENST00000344624.8 | |
DROSHA | NM_013235.5 | c.3218A>C | p.Asp1073Ala | missense_variant, splice_region_variant | 27/35 | ||
DROSHA | NM_001100412.2 | c.3107A>C | p.Asp1036Ala | missense_variant, splice_region_variant | 27/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DROSHA | ENST00000344624.8 | c.3218A>C | p.Asp1073Ala | missense_variant, splice_region_variant | 28/36 | 5 | NM_001382508.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000140 AC: 3AN: 214382Hom.: 0 AF XY: 0.0000174 AC XY: 2AN XY: 114650
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GnomAD4 exome AF: 0.00000417 AC: 6AN: 1439876Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3AN XY: 713604
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hepatoblastoma Uncertain:1
Uncertain significance, no assertion criteria provided | research | Molecular Oncology - Human Genetics Lab, University of Sao Paulo | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;B;.
Vest4
MutPred
Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at