rs116551057
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_000081.4(LYST):c.4548C>T(p.Ser1516=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,612,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: đť‘“ 0.0010 ( 0 hom., cov: 32)
Exomes đť‘“: 0.000092 ( 1 hom. )
Consequence
LYST
NM_000081.4 synonymous
NM_000081.4 synonymous
Scores
11
Clinical Significance
Conservation
PhyloP100: 0.0860
Genes affected
LYST (HGNC:1968): (lysosomal trafficking regulator) This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006029457).
BP6
?
Variant 1-235788841-G-A is Benign according to our data. Variant chr1-235788841-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 702188.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=1}. Variant chr1-235788841-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.086 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/152112) while in subpopulation AFR AF= 0.00357 (148/41496). AF 95% confidence interval is 0.0031. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYST | NM_000081.4 | c.4548C>T | p.Ser1516= | synonymous_variant | 13/53 | ENST00000389793.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYST | ENST00000389793.7 | c.4548C>T | p.Ser1516= | synonymous_variant | 13/53 | 5 | NM_000081.4 | P1 | |
LYST | ENST00000489585.5 | c.4548C>T | p.Ser1516= | synonymous_variant, NMD_transcript_variant | 13/23 | 1 | |||
LYST | ENST00000492844.1 | n.8C>T | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
LYST | ENST00000697178.1 | c.4121C>T | p.Ala1374Val | missense_variant, NMD_transcript_variant | 12/52 |
Frequencies
GnomAD3 genomes ? AF: 0.00103 AC: 157AN: 151994Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000255 AC: 64AN: 250636Hom.: 0 AF XY: 0.000207 AC XY: 28AN XY: 135454
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GnomAD4 exome AF: 0.0000924 AC: 135AN: 1460866Hom.: 1 Cov.: 31 AF XY: 0.0000812 AC XY: 59AN XY: 726796
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GnomAD4 genome ? AF: 0.00103 AC: 157AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.000941 AC XY: 70AN XY: 74354
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
Vest4
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at