rs34642241

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000081.4(LYST):c.7793T>A(p.Phe2598Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00413 in 1,612,650 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F2598L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 119 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 106 hom. )

Consequence

LYST
NM_000081.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.87

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002840668).

BP6

Variant 1-235746515-A-T is Benign according to our data. Variant chr1-235746515-A-T is described in ClinVar as Benign. ClinVar VariationId is 235582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.7793T>A	p.Phe2598Tyr	missense	Exon 29 of 53	NP_000072.2
	LYST	NM_001301365.1		c.7793T>A	p.Phe2598Tyr	missense	Exon 29 of 53	NP_001288294.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LYST	ENST00000389793.7	TSL:5 MANE Select	c.7793T>A	p.Phe2598Tyr	missense	Exon 29 of 53	ENSP00000374443.2
LYST	ENST00000697241.1		c.2273T>A	p.Phe758Tyr	missense	Exon 13 of 26	ENSP00000513206.1
LYST	ENST00000487530.2	TSL:4	c.494T>A	p.Phe165Tyr	missense	Exon 4 of 4	ENSP00000417168.1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3318

AN:

152136

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0756

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00599

AC:

1499

AN:

250426

AF XY:

0.00436

show subpopulations

Gnomad AFR exome

AF:

0.0787

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00229

AC:

3342

AN:

1460396

Hom.:

106

Cov.:

AF XY:

0.00200

AC XY:

1454

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.0726

AC:

2425

AN:

33398

American (AMR)

AF:

0.00489

AC:

218

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.000197

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.0000750

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000272

AC:

302

AN:

1110942

Other (OTH)

AF:

0.00567

AC:

342

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0218

AC:

3322

AN:

152254

Hom.:

119

Cov.:

AF XY:

0.0206

AC XY:

1531

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0755

AC:

3136

AN:

41530

American (AMR)

AF:

0.00837

AC:

128

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68020

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00362

Hom.:

Bravo

AF:

0.0258

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0724

AC:

319

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00734

AC:

891

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000475

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Chédiak-Higashi syndrome (2)

Autoinflammatory syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.036

Eigen_PC

Benign

0.033

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

4.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Benign

0.080

Sift4G

Uncertain

0.039

Polyphen

0.93

Vest4

0.37

MVP

0.71

ClinPred

0.034

GERP RS

1.3

Varity_R

0.11

gMVP

0.24

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over