rs145329776

Variant names:

• chr11-24983267-C-G
• rs145329776
• NM_001009909.4:c.739C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-24983267-C-G
• chr11-24983267-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001009909.4(LUZP2):​c.739C>G​(p.Leu247Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,611,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: LUZP2 NM_001009909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02798286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009909.4. 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
	LUZP2	NM_001009909.4	MANE Select	c.739C>G	p.Leu247Val	missense	Exon 9 of 12	NP_001009909.2	Q86TE4-1
	LUZP2	NM_001252010.2		c.613C>G	p.Leu205Val	missense	Exon 7 of 10	NP_001238939.1
	LUZP2	NM_001252008.2		c.481C>G	p.Leu161Val	missense	Exon 9 of 12	NP_001238937.1	Q86TE4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP2	ENST00000336930.11	TSL:1 MANE Select	c.739C>G	p.Leu247Val	missense	Exon 9 of 12	ENSP00000336817.6	Q86TE4-1
	LUZP2	ENST00000533227.5	TSL:1	c.481C>G	p.Leu161Val	missense	Exon 9 of 12	ENSP00000432952.1	Q86TE4-4
	LUZP2	ENST00000620308.1	TSL:5	c.481C>G	p.Leu161Val	missense	Exon 8 of 11	ENSP00000480441.1	Q86TE4-4

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151782 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250212 AF XY: 0.0000961

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1459940 Hom.: 0 Cov.: 31 AF XY: 0.000150 AC XY: 109 AN XY: 726276

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.000180 AC: 8 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.000196 AC: 218 AN: 1110784

Other (OTH) AF: 0.000133 AC: 8 AN: 60296

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151782 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74122

African (AFR) AF: 0.0000242 AC: 1 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67832

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000328

EpiControl AF: 0.000238

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	0.067
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.5
DANN	Benign	0.12
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.90	N
PhyloP100		1.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.035
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MVP		0.11
MPC		0.056
ClinPred		0.039	T
GERP RS		-1.3
Varity_R		0.028
gMVP		0.11
Mutation Taster		=95/5	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: rs145329776; hg19: chr11-25004813;