Genetic Variant LUZP4:p.Leu180Val (chrX-115306400-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016383.5(LUZP4):c.538C>G(p.Leu180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,175 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

LUZP4
NM_016383.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.909

Variant links:

Genes affected

LUZP4 (HGNC:24971): (leucine zipper protein 4) This gene encodes a leucine-zipper protein that was first defined as a cancer testis antigens. The encoded protein is an RNA binding protein that interacts with the mRNA export receptor nuclear RNA export factor 2. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

LUZP4 links:

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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=0.09532827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP4	NM_016383.5 link	c.538C>G	p.Leu180Val	missense_variant	Exon 4 of 4	ENST00000371920.4	NP_057467.1	Q9P127-1
LUZP4	NM_001318840.2 link	c.292C>G	p.Leu98Val	missense_variant	Exon 3 of 3		NP_001305769.1	Q9P127-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUZP4	ENST00000371920.4 link	c.538C>G	p.Leu180Val	missense_variant	Exon 4 of 4	1	NM_016383.5	ENSP00000360988.3		Q9P127-1
LUZP4	ENST00000371921.5 link	c.*182C>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000360989.1		Q5JX98

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111245

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33449

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097930

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363296

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111245

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33449

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.538C>G (p.L180V) alteration is located in exon 4 (coding exon 4) of the LUZP4 gene. This alteration results from a C to G substitution at nucleotide position 538, causing the leucine (L) at amino acid position 180 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0070

DANN

Benign

0.72

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.41

M_CAP

Benign

0.063

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.63

REVEL

Benign

0.24

Sift

Benign

0.45

Sift4G

Benign

0.29

Polyphen

0.83

Vest4

0.056

MutPred

0.23

Gain of loop (P = 0.0195);

MVP

0.59

MPC

0.030

ClinPred

0.14

GERP RS

-0.33

Varity_R

0.041

gMVP

0.0042

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