chr5-31429522-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001382508.1(DROSHA):c.3169C>T(p.Leu1057=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000968 in 1,611,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 1 hom. )
Consequence
DROSHA
NM_001382508.1 synonymous
NM_001382508.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.28
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 5-31429522-G-A is Benign according to our data. Variant chr5-31429522-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041551.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 148 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DROSHA | NM_001382508.1 | c.3169C>T | p.Leu1057= | synonymous_variant | 27/36 | ENST00000344624.8 | |
DROSHA | NM_013235.5 | c.3169C>T | p.Leu1057= | synonymous_variant | 26/35 | ||
DROSHA | NM_001100412.2 | c.3058C>T | p.Leu1020= | synonymous_variant | 26/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DROSHA | ENST00000344624.8 | c.3169C>T | p.Leu1057= | synonymous_variant | 27/36 | 5 | NM_001382508.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000973 AC: 148AN: 152042Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000950 AC: 236AN: 248312Hom.: 0 AF XY: 0.000935 AC XY: 126AN XY: 134724
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GnomAD4 exome AF: 0.000968 AC: 1413AN: 1459806Hom.: 1 Cov.: 30 AF XY: 0.000921 AC XY: 669AN XY: 726146
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GnomAD4 genome ? AF: 0.000973 AC: 148AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.000833 AC XY: 62AN XY: 74394
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DROSHA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 04, 2021 | 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). - |
Computational scores
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Name
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Benign
Cadd
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at