chr3-45828492-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_020347.4(LZTFL1):c.724A>G(p.Thr242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T242T) has been classified as Likely benign.
Frequency
Consequence
NM_020347.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTFL1 | NM_020347.4 | c.724A>G | p.Thr242Ala | missense_variant | 8/10 | ENST00000296135.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTFL1 | ENST00000296135.11 | c.724A>G | p.Thr242Ala | missense_variant | 8/10 | 1 | NM_020347.4 | P1 | |
ENST00000699185.1 | n.3796+1092T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000239 AC: 60AN: 251460Hom.: 1 AF XY: 0.000191 AC XY: 26AN XY: 135902
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461884Hom.: 1 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727242
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 242 of the LZTFL1 protein (p.Thr242Ala). This variant is present in population databases (rs751968807, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with LZTFL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 963919). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LZTFL1 protein function. 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. - |
LZTFL1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at