1-235450286-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_152490.5(B3GALNT2):c.1423C>T(p.Gln475*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q475Q) has been classified as Likely benign.
Frequency
Consequence
NM_152490.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
B3GALNT2 | ENST00000366600.8 | c.1423C>T | p.Gln475* | stop_gained | Exon 12 of 12 | 1 | NM_152490.5 | ENSP00000355559.3 | ||
TBCE | ENST00000642610.2 | c.*1524G>A | 3_prime_UTR_variant | Exon 17 of 17 | NM_003193.5 | ENSP00000494796.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461576Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727116
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 07, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 04, 2022 | This sequence change creates a premature translational stop signal (p.Gln475*) in the B3GALNT2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the B3GALNT2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with B3GALNT2-related conditions (PMID: 23453667). ClinVar contains an entry for this variant (Variation ID: 41939). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Pathogenic:1Other:1
not provided, no classification provided | literature only | Leiden Muscular Dystrophy pages (B3GALNT2) | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2023 | Nonsense variant predicted to result in protein truncation, as the last 26 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35456500, 35127920, 23453667) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at