rs3768067
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000081.4(LYST):c.368A>G(p.His123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,609,896 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H123Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_000081.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.368A>G | p.His123Arg | missense_variant | 5/53 | ENST00000389793.7 | NP_000072.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.368A>G | p.His123Arg | missense_variant | 5/53 | 5 | NM_000081.4 | ENSP00000374443.2 |
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152234Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000877 AC: 216AN: 246214Hom.: 1 AF XY: 0.000774 AC XY: 103AN XY: 133044
GnomAD4 exome AF: 0.000292 AC: 425AN: 1457544Hom.: 2 Cov.: 34 AF XY: 0.000295 AC XY: 214AN XY: 725080
GnomAD4 genome AF: 0.000348 AC: 53AN: 152352Hom.: 1 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74502
ClinVar
Submissions by phenotype
Chédiak-Higashi syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 16, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 12, 2017 | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at