Variant 11-25078615-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001009909.4(LUZP2):c.998C>T(p.Thr333Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LUZP2
NM_001009909.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.252

Variant links:

Genes affected

LUZP2 (HGNC:23206): (leucine zipper protein 2) This gene encodes a leucine zipper protein. This protein is deleted in some patients with Wilms tumor-Aniridia-Genitourinary anomalies-mental Retardation (WAGR) syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

LUZP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046881378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LUZP2	NM_001009909.4 linkuse as main transcript	c.998C>T	p.Thr333Ile	missense_variant	12/12	ENST00000336930.11	NP_001009909.2
LUZP2	NM_001252010.2 linkuse as main transcript	c.872C>T	p.Thr291Ile	missense_variant	10/10		NP_001238939.1
LUZP2	NM_001252008.2 linkuse as main transcript	c.740C>T	p.Thr247Ile	missense_variant	12/12		NP_001238937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP2	ENST00000336930.11 linkuse as main transcript	c.998C>T	p.Thr333Ile	missense_variant	12/12	1	NM_001009909.4	ENSP00000336817	P1	Q86TE4-1
LUZP2	ENST00000533227.5 linkuse as main transcript	c.740C>T	p.Thr247Ile	missense_variant	12/12	1		ENSP00000432952		Q86TE4-4
LUZP2	ENST00000620308.1 linkuse as main transcript	c.740C>T	p.Thr247Ile	missense_variant	11/11	5		ENSP00000480441		Q86TE4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249082

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000497

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459718

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.998C>T (p.T333I) alteration is located in exon 12 (coding exon 12) of the LUZP2 gene. This alteration results from a C to T substitution at nucleotide position 998, causing the threonine (T) at amino acid position 333 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.55

T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.040

Sift

Benign

0.21

T;T;.

Sift4G

Benign

0.29

T;T;T

Polyphen

0.34

B;.;.

Vest4

0.019

MutPred

0.092

Loss of phosphorylation at T333 (P = 0.0243);.;.;

MVP

0.15

MPC

0.14

ClinPred

0.050

GERP RS

0.085

Varity_R

0.046

gMVP

0.090

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