Variant 1-235775088-TAA-TAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000081.4(LYST):c.5461-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,114,534 control chromosomes in the GnomAD database, including 45 homozygotes. 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 0.011 ( 19 hom., cov: 32)

Exomes 𝑓: 0.044 ( 26 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 0.462

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 Benign. Variant got -9 ACMG points.

BP6

Variant 1-235775088-T-TA is Benign according to our data. Variant chr1-235775088-T-TA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211409.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=2}.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.5461-3dupT		splice_region_variant, intron_variant	Intron 17 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.5461-3_5461-2insT		splice_region_variant, intron_variant	Intron 17 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1626

AN:

146176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00284

Gnomad AMI

AF:

0.00552

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.00678

Gnomad EAS

AF:

0.000983

Gnomad SAS

AF:

0.0192

Gnomad FIN

AF:

0.0168

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.00906

GnomAD3 exomes

AF:

0.0521

AC:

5054

AN:

96916

Hom.:

AF XY:

0.0521

AC XY:

2663

AN XY:

51150

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.0125

Gnomad SAS exome

AF:

0.0702

Gnomad FIN exome

AF:

0.0522

Gnomad NFE exome

AF:

0.0426

Gnomad OTH exome

AF:

0.0507

GnomAD4 exome

AF:

0.0438

AC:

42404

AN:

968306

Hom.:

Cov.:

AF XY:

0.0428

AC XY:

20542

AN XY:

480436

show subpopulations

Gnomad4 AFR exome

AF:

0.0266

Gnomad4 AMR exome

AF:

0.0645

Gnomad4 ASJ exome

AF:

0.0302

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.0437

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0454

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0111

AC:

1627

AN:

146228

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

817

AN XY:

71144

show subpopulations

Gnomad4 AFR

AF:

0.00283

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.00678

Gnomad4 EAS

AF:

0.000986

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0168

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.00897

Bravo

AF:

0.0107

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:2

Jun 16, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 11, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autoinflammatory syndrome

Uncertain:1

May 16, 2017

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Chédiak-Higashi syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

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