chr10-101003529-G-T

Variant names:

• chr10-101003529-G-T
• rs201744734
• NM_001318100.2:c.431G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001318100.2(LZTS2):​c.431G>T​(p.Arg144Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,371,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.98
• 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 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.431G>T	p.Arg144Leu	missense	Exon 3 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.431G>T	p.Arg144Leu	missense	Exon 3 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.431G>T	p.Arg144Leu	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.431G>T	p.Arg144Leu	missense	Exon 3 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.431G>T	p.Arg144Leu	missense	Exon 2 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.431G>T	p.Arg144Leu	missense	Exon 3 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1371010 Hom.: 0 Cov.: 31 AF XY: 0.00000595 AC XY: 4 AN XY: 671794

African (AFR) AF: 0.00 AC: 0 AN: 30558

American (AMR) AF: 0.00 AC: 0 AN: 30968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20138

East Asian (EAS) AF: 0.00 AC: 0 AN: 38896

South Asian (SAS) AF: 0.00 AC: 0 AN: 71368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5320

European-Non Finnish (NFE) AF: 0.00000749 AC: 8 AN: 1067754

Other (OTH) AF: 0.00 AC: 0 AN: 56392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.50	P
Vest4		0.93
MutPred		0.53		Loss of MoRF binding (P = 0.0066)
MVP		0.78
MPC		0.34
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.70
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs201744734; hg19: chr10-102763286;