chr12-69350257-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2
The NM_000239.3(LYZ):c.286C>A(p.His96Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000239.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYZ | NM_000239.3 | c.286C>A | p.His96Asn | missense_variant | 2/4 | ENST00000261267.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYZ | ENST00000261267.7 | c.286C>A | p.His96Asn | missense_variant | 2/4 | 1 | NM_000239.3 | P1 | |
LYZ | ENST00000549690.1 | c.286C>A | p.His96Asn | missense_variant | 2/3 | 2 | |||
LYZ | ENST00000548839.1 | c.286C>A | p.His96Asn | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251358Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135834
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461790Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727206
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74442
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 20, 2023 | The c.286C>A (p.H96N) alteration is located in exon 2 (coding exon 2) of the LYZ gene. This alteration results from a C to A substitution at nucleotide position 286, causing the histidine (H) at amino acid position 96 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with LYZ-related conditions. This variant is present in population databases (rs150655870, gnomAD 0.02%). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 96 of the LYZ protein (p.His96Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at