rs143599552
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_031407.7(HUWE1):c.12860C>T(p.Ser4287Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,208,182 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_031407.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.12860C>T | p.Ser4287Phe | missense_variant | 83/84 | ENST00000262854.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HUWE1 | ENST00000262854.11 | c.12860C>T | p.Ser4287Phe | missense_variant | 83/84 | 1 | NM_031407.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000902 AC: 1AN: 110919Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33097
GnomAD4 exome AF: 0.00000273 AC: 3AN: 1097263Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1AN XY: 362661
GnomAD4 genome ? AF: 0.00000902 AC: 1AN: 110919Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33097
ClinVar
Submissions by phenotype
Intellectual disability, X-linked syndromic, Turner type Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genomics Laboratory, Washington University in St. Louis | Jul 17, 2023 | The HUWE1 c.12860C>T (p.Ser4287Phe) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters. This variant is absent from the general population (gnomAD v.2.1.1), but is observed on 1/10,563 alleles in the ESP 6500, indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on HUWE1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at