NM_000081.4:c.5373G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000081.4(LYST):c.5373G>A(p.Lys1791Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,612,208 control chromosomes in the GnomAD database, including 123,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13097 hom., cov: 31)

Exomes 𝑓: 0.38 ( 110677 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.621

Publications

14 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

LYST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-235777150-C-T is Benign according to our data. Variant chr1-235777150-C-T is described in ClinVar as Benign. ClinVar VariationId is 254927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.621 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.5373G>A	p.Lys1791Lys	synonymous_variant	Exon 17 of 53	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.5373G>A	p.Lys1791Lys	synonymous_variant	Exon 17 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61329

AN:

151738

Hom.:

13083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.0626

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.344

AC:

86280

AN:

251078

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.0588

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.381

AC:

556878

AN:

1460352

Hom.:

110677

Cov.:

AF XY:

0.376

AC XY:

273142

AN XY:

726616

show subpopulations

African (AFR)

AF:

0.499

AC:

16672

AN:

33428

American (AMR)

AF:

0.284

AC:

12699

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

9545

AN:

26112

East Asian (EAS)

AF:

0.0856

AC:

3388

AN:

39598

South Asian (SAS)

AF:

0.205

AC:

17661

AN:

86242

European-Finnish (FIN)

AF:

0.434

AC:

23177

AN:

53404

Middle Eastern (MID)

AF:

0.324

AC:

1864

AN:

5756

European-Non Finnish (NFE)

AF:

0.405

AC:

449809

AN:

1110752

Other (OTH)

AF:

0.366

AC:

22063

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17515

35030

52544

70059

87574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13644

27288

40932

54576

68220

<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

AF:

0.404

AC:

61392

AN:

151856

Hom.:

13097

Cov.:

AF XY:

0.397

AC XY:

29477

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.493

AC:

20435

AN:

41444

American (AMR)

AF:

0.326

AC:

4972

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1248

AN:

3472

East Asian (EAS)

AF:

0.0628

AC:

325

AN:

5176

South Asian (SAS)

AF:

0.189

AC:

908

AN:

4816

European-Finnish (FIN)

AF:

0.433

AC:

4544

AN:

10496

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27674

AN:

67912

Other (OTH)

AF:

0.389

AC:

817

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1817

3634

5450

7267

9084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.409

Hom.:

8350

Bravo

AF:

0.401

Asia WGS

AF:

0.153

AC:

532

AN:

3468

EpiCase

AF:

0.391

EpiControl

AF:

0.399

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Jun 13, 2018

GeneDx

Significance: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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Chédiak-Higashi syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.2

(source)

DANN

Benign

0.56

PhyloP100

0.62

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over