chr5-31405728-TAAATA-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_001382508.1(DROSHA):c.3948-10_3948-6del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000195 in 1,430,738 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00020 ( 2 hom. )
Consequence
DROSHA
NM_001382508.1 splice_region, splice_polypyrimidine_tract, intron
NM_001382508.1 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.85
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 Benign. Variant got -12 ACMG points.
BP6
?
Variant 5-31405728-TAAATA-T is Benign according to our data. Variant chr5-31405728-TAAATA-T is described in ClinVar as [Likely_benign]. Clinvar id is 729434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DROSHA | NM_001382508.1 | c.3948-10_3948-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000344624.8 | |||
DROSHA | NM_001100412.2 | c.3837-10_3837-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
DROSHA | NM_013235.5 | c.3948-10_3948-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DROSHA | ENST00000344624.8 | c.3948-10_3948-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001382508.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 27AN: 147128Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000147 AC: 20AN: 136194Hom.: 0 AF XY: 0.000179 AC XY: 13AN XY: 72734
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GnomAD4 exome AF: 0.000196 AC: 251AN: 1283538Hom.: 2 AF XY: 0.000181 AC XY: 115AN XY: 636572
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GnomAD4 genome ? AF: 0.000190 AC: 28AN: 147200Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 11AN XY: 71456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DROSHA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2017 | - - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at