22-20993955-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006767.4(LZTR1):c.1385T>G(p.Ile462Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. I462T) has been classified as Uncertain significance.
Frequency
Consequence
NM_006767.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTR1 | NM_006767.4 | c.1385T>G | p.Ile462Ser | missense_variant | 13/21 | ENST00000646124.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTR1 | ENST00000646124.2 | c.1385T>G | p.Ile462Ser | missense_variant | 13/21 | NM_006767.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247974Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134450
GnomAD4 exome Cov.: 34
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2021 | 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. This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with serine at codon 462 of the LZTR1 protein (p.Ile462Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. 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