rs1556954998
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_031407.7(HUWE1):c.6301C>G(p.Leu2101Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
HUWE1
NM_031407.7 missense
NM_031407.7 missense
Scores
3
2
7
Clinical Significance
Conservation
PhyloP100: 7.75
Genes affected
HUWE1 (HGNC:30892): (HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1) This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]
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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;
PP2
?
Missense variant where missense usually causes diseases, HUWE1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30416963).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.6301C>G | p.Leu2101Val | missense_variant | 47/84 | ENST00000262854.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HUWE1 | ENST00000262854.11 | c.6301C>G | p.Leu2101Val | missense_variant | 47/84 | 1 | NM_031407.7 | P2 | |
HUWE1 | ENST00000342160.7 | c.6301C>G | p.Leu2101Val | missense_variant | 46/83 | 5 | P2 | ||
HUWE1 | ENST00000612484.4 | c.6274C>G | p.Leu2092Val | missense_variant | 44/81 | 5 | A2 | ||
HUWE1 | ENST00000704099.1 | c.6298C>G | p.Leu2100Val | missense_variant | 46/83 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 17, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
Sift4G
Benign
T;T;T
Polyphen
0.96
.;P;P
Vest4
MutPred
0.28
.;Gain of methylation at K2103 (P = 0.0861);Gain of methylation at K2103 (P = 0.0861);
MVP
MPC
1.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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