rs119473032
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_021020.5(LZTS1):āc.355A>Gā(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 š: 7.7e-7 ( 0 hom. )
Consequence
LZTS1
NM_021020.5 missense
NM_021020.5 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 5.49
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LZTS1 | NM_021020.5 | c.355A>G | p.Lys119Glu | missense_variant | 3/4 | ENST00000381569.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LZTS1 | ENST00000381569.5 | c.355A>G | p.Lys119Glu | missense_variant | 3/4 | 5 | NM_021020.5 | P1 | |
LZTS1 | ENST00000265801.6 | c.355A>G | p.Lys119Glu | missense_variant | 2/3 | 1 | P1 | ||
LZTS1 | ENST00000522290.5 | c.355A>G | p.Lys119Glu | missense_variant | 2/4 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 7.67e-7 AC: 1AN: 1303690Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 633382
GnomAD4 exome
AF:
AC:
1
AN:
1303690
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
633382
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Esophageal squamous cell carcinoma, somatic Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 30, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
T;T;T
Polyphen
P;P;D
Vest4
MutPred
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
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at