X-53546527-G-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_031407.7(HUWE1):c.10824C>G(p.Leu3608=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,207,255 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 46 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 0.00017 ( 0 hom., 6 hem., cov: 22)
Exomes 𝑓: 0.00010 ( 0 hom. 40 hem. )
Consequence
HUWE1
NM_031407.7 synonymous
NM_031407.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0320
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant X-53546527-G-C is Benign according to our data. Variant chrX-53546527-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 211158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.032 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00017 (19/111959) while in subpopulation EAS AF= 0.00532 (19/3572). AF 95% confidence interval is 0.00348. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.10824C>G | p.Leu3608= | synonymous_variant | 70/84 | ENST00000262854.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HUWE1 | ENST00000262854.11 | c.10824C>G | p.Leu3608= | synonymous_variant | 70/84 | 1 | NM_031407.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000170 AC: 19AN: 111907Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6AN XY: 34055
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GnomAD3 exomes AF: 0.000408 AC: 73AN: 179031Hom.: 0 AF XY: 0.000392 AC XY: 25AN XY: 63705
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GnomAD4 exome AF: 0.000105 AC: 115AN: 1095296Hom.: 0 Cov.: 31 AF XY: 0.000111 AC XY: 40AN XY: 360716
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GnomAD4 genome ? AF: 0.000170 AC: 19AN: 111959Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6AN XY: 34117
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 09, 2019 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2017 | This alteration is classified as 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 29, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at