Variant 8-20249833-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_021020.5(LZTS1):c.1680G>A(p.Leu560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00049 in 1,614,232 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

LZTS1
NM_021020.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 8-20249833-C-T is Benign according to our data. Variant chr8-20249833-C-T is described in ClinVar as [Benign]. Clinvar id is 1674665.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.62 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZTS1	NM_021020.5 linkuse as main transcript	c.1680G>A	p.Leu560=	synonymous_variant	4/4	ENST00000381569.5	NP_066300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZTS1	ENST00000381569.5 linkuse as main transcript	c.1680G>A	p.Leu560=	synonymous_variant	4/4	5	NM_021020.5	ENSP00000370981	P1	Q9Y250-1
LZTS1	ENST00000265801.6 linkuse as main transcript	c.1680G>A	p.Leu560=	synonymous_variant	3/3	1		ENSP00000265801	P1	Q9Y250-1
LZTS1	ENST00000522290.5 linkuse as main transcript	c.1503G>A	p.Leu501=	synonymous_variant	4/4	1		ENSP00000429263		Q9Y250-4

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00790

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00115

AC:

289

AN:

251350

Hom.:

AF XY:

0.00117

AC XY:

159

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00261

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00832

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000459

AC:

671

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00267

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00741

Gnomad4 NFE exome

AF:

0.0000800

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152348

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00790

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000230

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.9

DANN

Benign

0.74

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