1-1232281-G-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_080605.4(B3GALT6):c.3G>A(p.Met1?) variant causes a start lost change. 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 (★).
Frequency
Genomes: not found (cov: 33)
Consequence
B3GALT6
NM_080605.4 start_lost
NM_080605.4 start_lost
Scores
6
1
9
Clinical Significance
Conservation
PhyloP100: 4.79
Genes affected
B3GALT6 (HGNC:17978): (beta-1,3-galactosyltransferase 6) The enzyme encoded by this intronless gene is a beta-1,3-galactosyltransferase found in the medial Golgi apparatus, where it catalyzes the transfer of galactose from UDP-galactose to substrates containing a terminal beta-linked galactose moiety. The encoded enzyme has a particular affinity for galactose-beta-1,4-xylose found in the linker region of glycosamines. This enzyme is required for glycosaminoglycan synthesis. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_080605.4 (B3GALT6) was described as [Likely_pathogenic] in ClinVar as 1452181
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-1232281-G-A is Pathogenic according to our data. Variant chr1-1232281-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2151860.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondyloepimetaphyseal dysplasia with joint laxity;C3809210:Ehlers-Danlos syndrome, spondylodysplastic type, 2 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 04, 2023 | This sequence change affects the initiator methionine of the B3GALT6 mRNA. The next in-frame methionine is located at codon 42. 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. Disruption of the initiator codon has been observed in individuals with B3GALT6-related conditions (PMID: 23664117, 29931299). ClinVar contains an entry for this variant (Variation ID: 2151860). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects B3GALT6 function (PMID: 23664117). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Pathogenic
.;D
Sift4G
Pathogenic
.;D
Polyphen
B;B
Vest4
0.77
MutPred
Loss of disorder (P = 0.0562);Loss of disorder (P = 0.0562);
MVP
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.