chr12-69353154-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_000239.3(LYZ):c.382G>A(p.Val128Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000239.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYZ | NM_000239.3 | c.382G>A | p.Val128Met | missense_variant, splice_region_variant | 4/4 | ENST00000261267.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYZ | ENST00000261267.7 | c.382G>A | p.Val128Met | missense_variant, splice_region_variant | 4/4 | 1 | NM_000239.3 | P1 | |
LYZ | ENST00000549690.1 | c.303G>A | p.Gly101= | splice_region_variant, synonymous_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251428Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135900
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1459666Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726376
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 128 of the LYZ protein (p.Val128Met). This variant is present in population databases (rs551709281, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LYZ-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at