Genetic Variant LYST:c.11268-5dupT (chr1-235663082-T-TA) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1

The NM_000081.4(LYST):c.11268-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 0)

Exomes 𝑓: 0.017 ( 0 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.694

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 1-235663082-T-TA is Benign according to our data. Variant chr1-235663082-T-TA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 296343.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000261 (39/149444) while in subpopulation EAS AF= 0.00237 (12/5056). AF 95% confidence interval is 0.00137. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.11268-5dupT		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
LYST	ENST00000389793.7 link	c.11268-5_11268-4insT		splice_region_variant, intron_variant	Intron 52 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.000261

AC:

AN:

149358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00237

Gnomad SAS

AF:

0.000851

Gnomad FIN

AF:

0.000404

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000164

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0168

AC:

19516

AN:

1163230

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

9447

AN XY:

582630

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.00839

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.000261

AC:

AN:

149444

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

72798

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000470

Gnomad4 ASJ

AF:

0.000291

Gnomad4 EAS

AF:

0.00237

Gnomad4 SAS

AF:

0.000854

Gnomad4 FIN

AF:

0.000404

Gnomad4 NFE

AF:

0.000164

Gnomad4 OTH

AF:

0.00

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

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autoinflammatory syndrome

Benign:1

Aug 01, 2018

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-235663082-TAAAA-TAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over