rs33998267

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000081.4(LYST):c.9C>T(p.Thr3Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,611,378 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.011 ( 8 hom., cov: 32)

Exomes 𝑓: 0.016 ( 212 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.148

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-235830409-G-A is Benign according to our data. Variant chr1-235830409-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 254942.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=4, Uncertain_significance=1}. Variant chr1-235830409-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.148 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0115 (1745/151914) while in subpopulation AMR AF= 0.0184 (280/15250). AF 95% confidence interval is 0.0166. There are 8 homozygotes in gnomad4. There are 794 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.9C>T	p.Thr3Thr	synonymous_variant	Exon 3 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.9C>T	p.Thr3Thr	synonymous_variant	Exon 3 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1746

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.00723

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0226

GnomAD3 exomes

AF:

0.0115

AC:

2859

AN:

249432

Hom.:

AF XY:

0.0116

AC XY:

1563

AN XY:

134846

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00211

Gnomad FIN exome

AF:

0.00704

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.0158

AC:

23033

AN:

1459464

Hom.:

212

Cov.:

AF XY:

0.0154

AC XY:

11159

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.00240

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00295

Gnomad4 FIN exome

AF:

0.00806

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0115

AC:

1745

AN:

151914

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

794

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00282

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00313

Gnomad4 FIN

AF:

0.00723

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0127

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0163

EpiControl

AF:

0.0170

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Chédiak-Higashi syndrome

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

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

- -

not specified

Benign:2

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:1

May 05, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome

Benign:1

May 26, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.49

CADD

Benign

1.5

DANN

Benign

0.85

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