rs767361165
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_194318.4(B3GLCT):c.459+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.0000191 in 1,517,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
B3GLCT
NM_194318.4 splice_donor
NM_194318.4 splice_donor
Scores
5
1
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
B3GLCT (HGNC:20207): (beta 3-glucosyltransferase) The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-31247967-G-A is Pathogenic according to our data. Variant chr13-31247967-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 449340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-31247967-G-A is described in Lovd as [Likely_pathogenic]. Variant chr13-31247967-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
B3GLCT | NM_194318.4 | c.459+1G>A | splice_donor_variant | ENST00000343307.5 | NP_919299.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
B3GLCT | ENST00000343307.5 | c.459+1G>A | splice_donor_variant | 1 | NM_194318.4 | ENSP00000343002 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250688Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135568
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GnomAD4 exome AF: 0.0000205 AC: 28AN: 1364958Hom.: 0 Cov.: 22 AF XY: 0.0000234 AC XY: 16AN XY: 684840
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74320
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2017 | - - |
Peters plus syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2009 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2018 | The c.459+1G>A pathogenic variant in the B3GALTL gene has been reported previously in a patient with Peters plus syndrome who also harbored the c.660+1G>A pathogenic variant (Reis et al., 2008). This splice site variant destroys the canonical splice donor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.459+1G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.459+1G>A as a pathogenic variant - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D
GERP RS
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at