GeneBe

chr1-235663082-TAAAA-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000081.4(LYST):​c.11268-8_11268-5delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,152 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56

Publications

0 publications found
Variant links:
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]
LYST Gene-Disease associations (from GenCC):
  • Chediak-Higashi syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
  • attenuated Chédiak-Higashi syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LYSTNM_000081.4 linkc.11268-8_11268-5delTTTT splice_region_variant, intron_variant Intron 52 of 52 ENST00000389793.7 NP_000072.2 Q99698-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LYSTENST00000389793.7 linkc.11268-8_11268-5delTTTT splice_region_variant, intron_variant Intron 52 of 52 5 NM_000081.4 ENSP00000374443.2 Q99698-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
8.24e-7
AC:
1
AN:
1213152
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
610296
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25932
American (AMR)
AF:
0.00
AC:
0
AN:
39804
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22974
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33506
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77740
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47120
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4854
European-Non Finnish (NFE)
AF:
0.00000110
AC:
1
AN:
909952
Other (OTH)
AF:
0.00
AC:
0
AN:
51270
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.29
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.29
Position offset: -42

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs36014994; hg19: chr1-235826382; API