rs1557036757
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_031407.7(HUWE1):c.344C>T(p.Ser115Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_031407.7 missense
Scores
Clinical Significance
Conservation
Publications
- intellectual disability, X-linked syndromic, Turner typeInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P
- non-syndromic X-linked intellectual disabilityInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- syndromic intellectual disabilityInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.344C>T | p.Ser115Phe | missense_variant | Exon 6 of 84 | ENST00000262854.11 | NP_113584.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
X-linked intellectual disability Pathogenic:1
This variant has been previously reported as a de novo change in a female patient with X-linked intellectual disability (PMID: 29180823). That reported patient had abnormal X-inactivation studies (PMID: 29180823). It is absent from the gnomAD population database and thus is presumed to be rare. The c.344C>T (p.Ser115Phe) variant is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.344C>T (p.Ser115Phe) variant is classified as Likely Pathogenic. -
Intellectual disability, X-linked syndromic, Turner type Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at