chr10-72008083-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_004273.5(CHST3):c.1052C>A(p.Ser351Tyr) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S351F) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004273.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHST3 | NM_004273.5 | c.1052C>A | p.Ser351Tyr | missense_variant | 3/3 | ENST00000373115.5 | |
CHST3 | XM_006718075.5 | c.1052C>A | p.Ser351Tyr | missense_variant | 3/3 | ||
CHST3 | XM_011540369.3 | c.1052C>A | p.Ser351Tyr | missense_variant | 3/3 | ||
CHST3 | XM_047426022.1 | c.1052C>A | p.Ser351Tyr | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHST3 | ENST00000373115.5 | c.1052C>A | p.Ser351Tyr | missense_variant | 3/3 | 1 | NM_004273.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1393272Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 686952
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Spondyloepiphyseal dysplasia with congenital joint dislocations Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Nov 15, 2018 | The homozygous p.Ser351Tyr variant in CHST3 was identified by our study in one individual with Spondyloepiphyseal Dysplasia with Congenital Joint Dislocations. This variant was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. An additional variant at the same position, p.Ser351Phe), has been reported in ClinVar as without any disease association, slightly supporting that a change at this position may not be tolerated (ClinVar ID: 377035). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Ser351Tyr variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at