rs113209379

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_000081.4(LYST):c.8027G>T(p.Ser2676Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,600,428 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

LYST
NM_000081.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:3

Conservation

PhyloP100: 0.571

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp
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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01042375).

BP6

Variant 1-235744103-C-A is Benign according to our data. Variant chr1-235744103-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435789.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000815 (124/152114) while in subpopulation AFR AF = 0.0028 (116/41492). AF 95% confidence interval is 0.00238. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.8027G>T	p.Ser2676Ile	missense	Exon 30 of 53	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.8027G>T	p.Ser2676Ile	missense	Exon 30 of 53	NP_001288294.1	Q99698-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYST	ENST00000389793.7	TSL:5 MANE Select	c.8027G>T	p.Ser2676Ile	missense	Exon 30 of 53	ENSP00000374443.2	Q99698-1
LYST	ENST00000697241.1		c.2507G>T	p.Ser836Ile	missense	Exon 14 of 26	ENSP00000513206.1	A0A8V8TM69
LYST	ENST00000475277.2	TSL:5	c.122G>T	p.Ser41Ile	missense	Exon 2 of 15	ENSP00000513164.1	A0A8V8TM32

Frequencies

GnomAD3 genomes

AF:

0.000796

AC:

121

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000199

AC:

AN:

251134

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000987

AC:

143

AN:

1448314

Hom.:

Cov.:

AF XY:

0.0000873

AC XY:

AN XY:

721412

show subpopulations

African (AFR)

AF:

0.00314

AC:

104

AN:

33124

American (AMR)

AF:

0.000134

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26024

East Asian (EAS)

AF:

0.00

AC:

AN:

39462

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100006

Other (OTH)

AF:

0.000517

AC:

AN:

59910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000815

AC:

124

AN:

152114

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00280

AC:

116

AN:

41492

American (AMR)

AF:

0.000524

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000587

Hom.:

Bravo

AF:

0.000990

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Chédiak-Higashi syndrome (2)

Autoinflammatory syndrome (1)

LYST-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.20

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.41

M_CAP

Benign

0.037

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PhyloP100

0.57

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

REVEL

Benign

0.12

Sift

Benign

0.057

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.25

MVP

0.57

ClinPred

0.031

GERP RS

2.8

Varity_R

0.091

gMVP

0.31

Mutation Taster

=80/20

polymorphism

(source)

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

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