9-33113555-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001497.4(B4GALT1):c.1096A>T(p.Met366Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000057 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. M366V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001497.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B4GALT1 | NM_001497.4 | c.1096A>T | p.Met366Leu | missense_variant | 6/6 | ENST00000379731.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B4GALT1 | ENST00000379731.5 | c.1096A>T | p.Met366Leu | missense_variant | 6/6 | 1 | NM_001497.4 | P1 | |
B4GALT1 | ENST00000535206.5 | c.649-8774A>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251466Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135906
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727248
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 366 of the B4GALT1 protein (p.Met366Leu). This variant is present in population databases (rs377678566, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with B4GALT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449848). 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) performed at Invitae indicates that this missense variant is not expected to disrupt B4GALT1 protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2017 | The M366L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M366L variant is observed in 9/66730 (0.01%) alleles from individuals of European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M366L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at