NM_001009909.4:c.739C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001009909.4(LUZP2):​c.739C>T​(p.Leu247Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,459,940 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. 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. L247P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LUZP2
NM_001009909.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07221243).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LUZP2NM_001009909.4 linkc.739C>T p.Leu247Phe missense_variant Exon 9 of 12 ENST00000336930.11 NP_001009909.2 Q86TE4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LUZP2ENST00000336930.11 linkc.739C>T p.Leu247Phe missense_variant Exon 9 of 12 1 NM_001009909.4 ENSP00000336817.6 Q86TE4-1
LUZP2ENST00000533227.5 linkc.481C>T p.Leu161Phe missense_variant Exon 9 of 12 1 ENSP00000432952.1 Q86TE4-4
LUZP2ENST00000620308.1 linkc.481C>T p.Leu161Phe missense_variant Exon 8 of 11 5 ENSP00000480441.1 Q86TE4-4
LUZP2ENST00000529015.5 linkc.*85C>T downstream_gene_variant 4 ENSP00000437032.1 E9PP05

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250212
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135248
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1459940
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726276
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.075
T;.;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.38
T;.;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.072
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.5
N;N;.
REVEL
Benign
0.099
Sift
Uncertain
0.024
D;D;.
Sift4G
Uncertain
0.016
D;D;D
Polyphen
0.0
B;.;.
Vest4
0.061
MutPred
0.058
Gain of methylation at K246 (P = 0.0292);.;.;
MVP
0.099
MPC
0.071
ClinPred
0.088
T
GERP RS
-1.3
Varity_R
0.050
gMVP
0.17

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.

Other links and lift over

dbSNP: rs145329776; hg19: chr11-25004813; API