Variant rs3768066 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000081.4(LYST):c.2355T>C(p.Leu785=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,112 control chromosomes in the GnomAD database, including 13,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 973 hom., cov: 31)

Exomes 𝑓: 0.13 ( 12773 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0390

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-235808463-A-G is Benign according to our data. Variant chr1-235808463-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 254915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4 linkuse as main transcript	c.2355T>C	p.Leu785=	synonymous_variant	5/53	ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7 linkuse as main transcript	c.2355T>C	p.Leu785=	synonymous_variant	5/53	5	NM_000081.4	P1	Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16255

AN:

151454

Hom.:

975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0435

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.105

AC:

26266

AN:

250712

Hom.:

1545

AF XY:

0.104

AC XY:

14145

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0882

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.0494

Gnomad SAS exome

AF:

0.0413

Gnomad FIN exome

AF:

0.0965

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.128

AC:

186892

AN:

1460542

Hom.:

12773

Cov.:

AF XY:

0.126

AC XY:

91613

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.0707

Gnomad4 AMR exome

AF:

0.0909

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.0495

Gnomad4 SAS exome

AF:

0.0420

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.107

AC:

16251

AN:

151570

Hom.:

973

Cov.:

AF XY:

0.103

AC XY:

7629

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.0709

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.0436

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.136

Hom.:

1973

Bravo

AF:

0.109

Asia WGS

AF:

0.0420

AC:

145

AN:

3476

EpiCase

AF:

0.150

EpiControl

AF:

0.148

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Chédiak-Higashi syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.71

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