dbSNP rs147094885: LYST:p.Ala2480Val (chr1-235753065-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000081.4(LYST):c.7439C>T(p.Ala2480Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2480D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LYST
NM_000081.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.38

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3166889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.7439C>T	p.Ala2480Val	missense_variant	Exon 26 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.7439C>T	p.Ala2480Val	missense_variant	Exon 26 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704526

African (AFR)

AF:

0.00

AC:

AN:

32464

American (AMR)

AF:

0.00

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25766

East Asian (EAS)

AF:

0.00

AC:

AN:

39296

South Asian (SAS)

AF:

0.00

AC:

AN:

85102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065366

Other (OTH)

AF:

0.00

AC:

AN:

58574

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.028

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.1

PhyloP100

9.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Benign

0.15

Sift

Benign

0.10

Sift4G

Uncertain

0.013

Polyphen

0.35

Vest4

0.39

MutPred

0.25

Loss of helix (P = 0.1299);

MVP

0.47

ClinPred

0.90

GERP RS

5.2

Varity_R

0.16

gMVP

0.27

Mutation Taster

=73/27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over