Genetic Variant LUZP4:p.Ser29Phe (chrX-115289845-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_016383.5(LUZP4):c.86C>T(p.Ser29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000592 in 1,183,384 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts 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: 22)

Exomes 𝑓: 0.0000056 ( 0 hom. 2 hem. )

Consequence

LUZP4
NM_016383.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31607658).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016383.5. 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
	LUZP4	NM_016383.5	MANE Select	c.86C>T	p.Ser29Phe	missense	Exon 1 of 4	NP_057467.1	Q9P127-1
	LUZP4	NM_001318840.2		c.-42C>T		5_prime_UTR	Exon 1 of 3	NP_001305769.1	Q9P127-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP4	ENST00000371920.4	TSL:1 MANE Select	c.86C>T	p.Ser29Phe	missense	Exon 1 of 4	ENSP00000360988.3	Q9P127-1
	LUZP4	ENST00000371921.5	TSL:2	c.86C>T	p.Ser29Phe	missense	Exon 1 of 3	ENSP00000360989.1	Q5JX98

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111275

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000277

AC:

AN:

180438

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000560

AC:

AN:

1072109

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

340243

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25914

American (AMR)

AF:

0.00

AC:

AN:

34989

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19141

East Asian (EAS)

AF:

0.0000668

AC:

AN:

29962

South Asian (SAS)

AF:

0.00

AC:

AN:

53135

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40173

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4065

European-Non Finnish (NFE)

AF:

0.00000488

AC:

AN:

819588

Other (OTH)

AF:

0.00

AC:

AN:

45142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000899

AC:

AN:

111275

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33505

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30559

American (AMR)

AF:

0.00

AC:

AN:

10473

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3525

South Asian (SAS)

AF:

0.00

AC:

AN:

2644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52951

Other (OTH)

AF:

0.00

AC:

AN:

1487

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.81

PhyloP100

2.3

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.19

Sift

Benign

0.13

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.66

MutPred

0.32

Loss of sheet (P = 7e-04)

MVP

0.96

MPC

0.023

ClinPred

0.48

GERP RS

2.5

PromoterAI

0.026

Neutral

(source)

Varity_R

0.16

gMVP

0.016

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over