rs149520131

Variant names:

• chr1-235809144-C-A
• NM_000081.4:c.1674G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235809144-C-A
• chr1-235809144-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000081.4(LYST):​c.1674G>T​(p.Leu558Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L558L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYST NM_000081.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17653006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.1674G>T	p.Leu558Phe	missense_variant	Exon 5 of 53	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.1674G>T	p.Leu558Phe	missense_variant	Exon 5 of 53	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.025
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.21
Sift	Benign	0.045	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.057	B;.
Vest4		0.31
MutPred		0.33		Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);
MVP		0.71
MPC		0.086
ClinPred		0.45	T
GERP RS		-5.2
Varity_R		0.11
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-235972444;