Genetic Variant LUZP4:p.Arg5Trp (chrX-115289772-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016383.5(LUZP4):c.13C>T(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,205,963 control chromosomes in the GnomAD database, including 1 homozygotes. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 56 hem. )

Consequence

LUZP4
NM_016383.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045647025).

BP6

Variant X-115289772-C-T is Benign according to our data. Variant chrX-115289772-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661248.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP4	NM_016383.5 link	c.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 4	ENST00000371920.4	NP_057467.1	Q9P127-1
LUZP4	NM_001318840.2 link	c.-115C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		NP_001305769.1	Q9P127-2
LUZP4	NM_001318840.2 link	c.-115C>T		5_prime_UTR_variant	Exon 1 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.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 4	1	NM_016383.5	ENSP00000360988.3		Q9P127-1
LUZP4	ENST00000371921.5 link	c.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 3	2		ENSP00000360989.1		Q5JX98

Frequencies

GnomAD3 genomes

AF:

0.000287

AC:

AN:

111376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00571

Gnomad SAS

AF:

0.000750

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000469

AC:

AN:

183250

AF XY:

0.000473

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00447

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000111

AC:

122

AN:

1094538

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

360072

show subpopulations

African (AFR)

AF:

0.000266

AC:

AN:

26317

American (AMR)

AF:

0.00

AC:

AN:

35157

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19330

East Asian (EAS)

AF:

0.00179

AC:

AN:

30129

South Asian (SAS)

AF:

0.000555

AC:

AN:

54015

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40367

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4085

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

839197

Other (OTH)

AF:

0.000631

AC:

AN:

45941

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000287

AC:

AN:

111425

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

33635

show subpopulations

African (AFR)

AF:

0.000326

AC:

AN:

30685

American (AMR)

AF:

0.00

AC:

AN:

10519

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00573

AC:

AN:

3493

South Asian (SAS)

AF:

0.000753

AC:

AN:

2656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52989

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LUZP4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.027

.;T

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PhyloP100

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.051

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.82

.;P

Vest4

0.034

MVP

0.68

MPC

0.024

ClinPred

0.040

GERP RS

0.97

PromoterAI

-0.45

Neutral

(source)

Varity_R

0.083

gMVP

0.0081

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over