dbSNP rs119473032: LZTS1:p.Lys119Glu (chr8-20253576-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_021020.5(LZTS1):c.355A>G(p.Lys119Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000767 in 1,303,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

LZTS1
NM_021020.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.49

Publications

4 publications found

Variant links:

Genes affected

LZTS1 (HGNC:13861): (leucine zipper tumor suppressor 1) This gene encodes a tumor suppressor protein that is ubiquitously expressed in normal tissues. In uveal melanomas, expression of this protein is silenced in rapidly metastasizing and metastatic tumor cells but has normal expression in slowly metastasizing or nonmetastasizing tumor cells. This protein may have a role in cell-cycle control by interacting with the Cdk1/cyclinB1 complex. This gene is located on chromosomal region 8p22. Loss of heterozygosity (LOH) in the 8p arm is a common characteristic of many types of cancer. [provided by RefSeq, Nov 2009]

LZTS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-20253576-T-C is Pathogenic according to our data. Variant chr8-20253576-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 4246.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS1	NM_021020.5 link	c.355A>G	p.Lys119Glu	missense_variant	Exon 3 of 4	ENST00000381569.5	NP_066300.1	Q9Y250-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LZTS1	ENST00000381569.5 link	c.355A>G	p.Lys119Glu	missense_variant	Exon 3 of 4	5	NM_021020.5	ENSP00000370981.1	Q9Y250-1
LZTS1	ENST00000265801.6 link	c.355A>G	p.Lys119Glu	missense_variant	Exon 2 of 3	1		ENSP00000265801.6	Q9Y250-1
LZTS1	ENST00000522290.5 link	c.355A>G	p.Lys119Glu	missense_variant	Exon 2 of 4	1		ENSP00000429263.1	Q9Y250-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.67e-7

AC:

AN:

1303690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

633382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29420

American (AMR)

AF:

0.00

AC:

AN:

22392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19232

East Asian (EAS)

AF:

0.00

AC:

AN:

35878

South Asian (SAS)

AF:

0.00

AC:

AN:

66464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5094

European-Non Finnish (NFE)

AF:

9.63e-7

AC:

AN:

1038104

Other (OTH)

AF:

0.00

AC:

AN:

54252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Esophageal squamous cell carcinoma, somatic

Pathogenic:1

Mar 30, 1999

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

T;.;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;M

PhyloP100

5.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.056

T;T;T

Polyphen

0.92

P;P;D

Vest4

0.79

MutPred

0.11

Loss of ubiquitination at K119 (P = 0.0017);Loss of ubiquitination at K119 (P = 0.0017);Loss of ubiquitination at K119 (P = 0.0017);

MVP

0.39

MPC

1.3

ClinPred

0.95

GERP RS

5.3

Varity_R

0.34

gMVP

0.65

Mutation Taster

=6/94

disease causing (ClinVar)

(source)

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

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rs119473032

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over