1-1232478-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_080605.4(B3GALT6):c.200C>T(p.Pro67Leu) variant causes a missense change involving the alteration of a non-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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67S) has been classified as Uncertain significance.
Frequency
Consequence
NM_080605.4 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 |
---|---|---|---|---|---|---|---|
B3GALT6 | NM_080605.4 | c.200C>T | p.Pro67Leu | missense_variant | 1/1 | ENST00000379198.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B3GALT6 | ENST00000379198.5 | c.200C>T | p.Pro67Leu | missense_variant | 1/1 | NM_080605.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 876386Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 408524
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 06, 2013 | - - |
Spondyloepimetaphyseal dysplasia with joint laxity;C3809210:Ehlers-Danlos syndrome, spondylodysplastic type, 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 27, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 67 of the B3GALT6 protein (p.Pro67Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This missense change has been observed in individual(s) with spondyloepimetaphyseal dysplasia with joint laxity (PMID: 23664117, 24766538). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 60489). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on B3GALT6 protein function. Experimental studies have shown that this missense change affects B3GALT6 function (PMID: 23664117). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at