rs199469653
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_003590.5(CUL3):c.1207-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CUL3
NM_003590.5 splice_region, intron
NM_003590.5 splice_region, intron
Scores
2
Splicing: ADA: 0.2380
2
Clinical Significance
Conservation
PhyloP100: 2.27
Genes affected
CUL3 (HGNC:2553): (cullin 3) This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-224503825-G-A is Pathogenic according to our data. Variant chr2-224503825-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 100519.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-224503825-G-A is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CUL3 | NM_003590.5 | c.1207-3C>T | splice_region_variant, intron_variant | Intron 8 of 15 | ENST00000264414.9 | NP_003581.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.25e-7 AC: 1AN: 1379776Hom.: 0 Cov.: 29 AF XY: 0.00000147 AC XY: 1AN XY: 681984
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1379776
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
681984
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Pseudohypoaldosteronism type 2A Pathogenic:1
-
Richard Lifton Laboratory, Yale University School of Medicine
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Pseudohypoaldosteronism type 2E Pathogenic:1
Jan 22, 2012
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at