rs999173078
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_194318.4(B3GLCT):āc.56T>Cā(p.Leu19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,359,576 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_194318.4 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 |
---|---|---|---|---|---|---|---|
B3GLCT | NM_194318.4 | c.56T>C | p.Leu19Pro | missense_variant | 1/15 | ENST00000343307.5 | |
B3GLCT | XM_011534936.2 | c.56T>C | p.Leu19Pro | missense_variant | 1/14 | ||
B3GLCT | XM_047430111.1 | c.56T>C | p.Leu19Pro | missense_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B3GLCT | ENST00000343307.5 | c.56T>C | p.Leu19Pro | missense_variant | 1/15 | 1 | NM_194318.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000173 AC: 26AN: 150110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 9AN: 70866Hom.: 0 AF XY: 0.000170 AC XY: 7AN XY: 41062
GnomAD4 exome AF: 0.000292 AC: 353AN: 1209466Hom.: 1 Cov.: 30 AF XY: 0.000255 AC XY: 152AN XY: 595222
GnomAD4 genome ? AF: 0.000173 AC: 26AN: 150110Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 11AN XY: 73248
ClinVar
Submissions by phenotype
Peters plus syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with B3GLCT-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces leucine with proline at codon 19 of the B3GLCT protein (p.Leu19Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.56T>C (p.L19P) alteration is located in exon 1 (coding exon 1) of the B3GLCT gene. This alteration results from a T to C substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at