1-235775088-TAA-TA

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_000081.4(LYST):c.5461-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,036,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.031 ( 0 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

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 -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-235775088-TA-T is Benign according to our data. Variant chr1-235775088-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 703786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235775088-TA-T is described in Lovd as [Benign]. Variant chr1-235775088-TA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000308 (45/145980) while in subpopulation AMR AF= 0.000614 (9/14662). AF 95% confidence interval is 0.000319. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.000308

AC:

AN:

145928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000614

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000212

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0551

AC:

5336

AN:

96916

Hom.:

AF XY:

0.0575

AC XY:

2943

AN XY:

51150

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.0626

Gnomad ASJ exome

AF:

0.0591

Gnomad EAS exome

AF:

0.0470

Gnomad SAS exome

AF:

0.0877

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0502

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0314

AC:

27947

AN:

890892

Hom.:

Cov.:

AF XY:

0.0308

AC XY:

13552

AN XY:

439346

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.0399

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.0235

Gnomad4 SAS exome

AF:

0.0350

Gnomad4 FIN exome

AF:

0.0321

Gnomad4 NFE exome

AF:

0.0310

Gnomad4 OTH exome

AF:

0.0305

GnomAD4 genome

AF:

0.000308

AC:

AN:

145980

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

70992

show subpopulations

Gnomad4 AFR

AF:

0.000299

Gnomad4 AMR

AF:

0.000614

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00112

Gnomad4 NFE

AF:

0.000212

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0694

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Chédiak-Higashi syndrome

Benign:2

Feb 07, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 22, 2019

GeneDx

Significance: 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.

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