rs144449744
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_031407.7(HUWE1):c.4503C>T(p.Pro1501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,204,481 control chromosomes in the GnomAD database, including 1 homozygotes. There are 467 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00090 ( 0 hom., 28 hem., cov: 23)
Exomes 𝑓: 0.0013 ( 1 hom. 439 hem. )
Consequence
HUWE1
NM_031407.7 synonymous
NM_031407.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.261
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant X-53588493-G-A is Benign according to our data. Variant chrX-53588493-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53588493-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.261 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 28 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.4503C>T | p.Pro1501= | synonymous_variant | 37/84 | ENST00000262854.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HUWE1 | ENST00000262854.11 | c.4503C>T | p.Pro1501= | synonymous_variant | 37/84 | 1 | NM_031407.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000900 AC: 100AN: 111120Hom.: 0 Cov.: 23 AF XY: 0.000840 AC XY: 28AN XY: 33316
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GnomAD3 exomes AF: 0.000843 AC: 145AN: 171996Hom.: 0 AF XY: 0.000921 AC XY: 53AN XY: 57562
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GnomAD4 exome AF: 0.00132 AC: 1438AN: 1093311Hom.: 1 Cov.: 30 AF XY: 0.00122 AC XY: 439AN XY: 359229
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GnomAD4 genome ? AF: 0.000900 AC: 100AN: 111170Hom.: 0 Cov.: 23 AF XY: 0.000839 AC XY: 28AN XY: 33376
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 21, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
HUWE1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 03, 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at