chr12-69350215-T-A
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PS1PM1PM2PP3_StrongPP5_Moderate
The NM_000239.3(LYZ):c.244T>A(p.Trp82Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.
Frequency
Consequence
NM_000239.3 missense
Scores
Clinical Significance
Conservation
Publications
- familial visceral amyloidosisInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- ALys amyloidosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LYZ | ENST00000261267.7 | c.244T>A | p.Trp82Arg | missense_variant | Exon 2 of 4 | 1 | NM_000239.3 | ENSP00000261267.2 | ||
LYZ | ENST00000549690.1 | c.244T>A | p.Trp82Arg | missense_variant | Exon 2 of 3 | 2 | ENSP00000449898.1 | |||
LYZ | ENST00000548839.1 | c.244T>A | p.Trp82Arg | missense_variant | Exon 2 of 2 | 2 | ENSP00000449969.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This variant is also known as W64R. This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 82 of the LYZ protein (p.Trp82Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with gastrointestinal amyloidosis (PMID: 12360495, 25217048). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 14378). 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 disruptive. For these reasons, this variant has been classified as Pathogenic. -
Familial visceral amyloidosis, Ostertag type Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at