1-235793511-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_000081.4(LYST):c.4108C>G(p.Pro1370Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000194 in 1,495,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P1370R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000081.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152050Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246586Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133272
GnomAD4 exome AF: 0.00000670 AC: 9AN: 1343012Hom.: 0 Cov.: 20 AF XY: 0.00000742 AC XY: 5AN XY: 673998
GnomAD4 genome AF: 0.000132 AC: 20AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74254
ClinVar
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:2
This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1370 of the LYST protein (p.Pro1370Ala). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 574882). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -
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Inborn genetic diseases Uncertain:1
The c.4108C>G (p.P1370A) alteration is located in exon 11 (coding exon 9) of the LYST gene. This alteration results from a C to G substitution at nucleotide position 4108, causing the proline (P) at amino acid position 1370 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at