chr10-101003637-C-T

Variant names:

• chr10-101003637-C-T
• rs764000155
• NM_001318100.2:c.539C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001318100.2(LZTS2):​c.539C>T​(p.Thr180Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000467 in 1,607,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07
• Publications: 0 publications found

Genes affected

LZTS2 (HGNC:29381): (leucine zipper tumor suppressor 2) The protein encoded by this gene belongs to the leucine zipper tumor suppressor family of proteins, which function in transcription regulation and cell cycle control. This family member can repress beta-catenin-mediated transcriptional activation and is a negative regulator of the Wnt signaling pathway. It negatively regulates microtubule severing at centrosomes, and is necessary for central spindle formation and cytokinesis completion. It is implicated in cancer, where it may inhibit cell proliferation and decrease susceptibility to tumor development. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16592568).
• BS2: High AC in GnomAdExome4 at 71 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	NM_001318100.2	MANE Select	c.539C>T	p.Thr180Met	missense	Exon 3 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.539C>T	p.Thr180Met	missense	Exon 3 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.539C>T	p.Thr180Met	missense	Exon 3 of 5	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.539C>T	p.Thr180Met	missense	Exon 3 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.539C>T	p.Thr180Met	missense	Exon 2 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.539C>T	p.Thr180Met	missense	Exon 3 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000487 AC: 12 AN: 246632 AF XY: 0.0000601

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000488 AC: 71 AN: 1455024 Hom.: 0 Cov.: 31 AF XY: 0.0000705 AC XY: 51 AN XY: 722966

African (AFR) AF: 0.0000598 AC: 2 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39616

South Asian (SAS) AF: 0.000515 AC: 44 AN: 85392

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52372

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108130

Other (OTH) AF: 0.0000166 AC: 1 AN: 60182

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74508

African (AFR) AF: 0.0000481 AC: 2 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000179 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.093
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.19		Loss of phosphorylation at T180 (P = 0.0485)
MVP		0.28
MPC		0.84
ClinPred		0.34	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.28
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs764000155; hg19: chr10-102763394; COSMIC: COSV64652619; COSMIC: COSV64652619;