chr8-20249748-C-G

Variant names:

• chr8-20249748-C-G
• rs910745164
• NM_021020.5:c.1765G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021020.5(LZTS1):​c.1765G>C​(p.Glu589Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LZTS1 NM_021020.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2840141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTS1	NM_021020.5	c.1765G>C	p.Glu589Gln	missense_variant	Exon 4 of 4	ENST00000381569.5	NP_066300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTS1	ENST00000381569.5	c.1765G>C	p.Glu589Gln	missense_variant	Exon 4 of 4	5	NM_021020.5	ENSP00000370981.1
LZTS1	ENST00000265801.6	c.1765G>C	p.Glu589Gln	missense_variant	Exon 3 of 3	1		ENSP00000265801.6
LZTS1	ENST00000522290.5	c.1588G>C	p.Glu530Gln	missense_variant	Exon 4 of 4	1		ENSP00000429263.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458150 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725486

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.089
Sift	Benign	0.077	T;T;T
Sift4G	Benign	0.094	T;T;T
Polyphen		0.89	P;P;P
Vest4		0.43
MutPred		0.42		Loss of disorder (P = 0.1033);Loss of disorder (P = 0.1033);.;
MVP		0.32
MPC		1.1
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.44

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

Other links and lift over

dbSNP: rs910745164; hg19: chr8-20107259; COSMIC: COSV56117519; COSMIC: COSV56117519;