rs148389013
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The NM_000081.4(LYST):c.10669G>T(p.Val3557Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,613,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign 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. V3557I) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.10669G>T | p.Val3557Leu | missense_variant | 47/53 | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.10669G>T | p.Val3557Leu | missense_variant | 47/53 | 5 | NM_000081.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251446Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135904
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460828Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726816
GnomAD4 genome AF: 0.000217 AC: 33AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74462
ClinVar
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3557 of the LYST protein (p.Val3557Leu). This variant is present in population databases (rs148389013, gnomAD 0.08%). 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: 576012). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.10669G>T (p.V3557L) alteration is located in exon 47 (coding exon 45) of the LYST gene. This alteration results from a G to T substitution at nucleotide position 10669, causing the valine (V) at amino acid position 3557 to be replaced by a leucine (L). 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 | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | LYST: PM2, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at