rs2070127
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The ENST00000264414.9(CUL3):c.1992A>T(p.Gln664His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q664Q) has been classified as Benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CUL3
ENST00000264414.9 missense
ENST00000264414.9 missense
Scores
7
12
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.82
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CUL3. . Gene score misZ 4.7538 (greater than the threshold 3.09). Trascript score misZ 5.1469 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, neurodevelopmental disorder with or without autism or seizures, pseudohypoaldosteronism type 2E.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUL3 | NM_003590.5 | c.1992A>T | p.Gln664His | missense_variant | 14/16 | ENST00000264414.9 | NP_003581.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUL3 | ENST00000264414.9 | c.1992A>T | p.Gln664His | missense_variant | 14/16 | 1 | NM_003590.5 | ENSP00000264414 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1438826Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 714326
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1438826
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
714326
Gnomad4 AFR exome
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Gnomad4 EAS exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N
REVEL
Uncertain
Sift
Benign
D;T;D;.;D
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;.;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0866);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at