Genetic Variant LUZP4:p.Arg73Gln (chrX-115302118-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016383.5(LUZP4):c.218G>A(p.Arg73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,183,423 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000093 ( 0 hom. 6 hem. )

Consequence

LUZP4
NM_016383.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.102

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05226785).

BP6

Variant X-115302118-G-A is Benign according to our data. Variant chrX-115302118-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2205924.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP4	NM_016383.5 link	c.218G>A	p.Arg73Gln	missense_variant	Exon 2 of 4	ENST00000371920.4	NP_057467.1	Q9P127-1
LUZP4	NM_001318840.2 link	c.91G>A	p.Gly31Arg	missense_variant	Exon 2 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.218G>A	p.Arg73Gln	missense_variant	Exon 2 of 4	1	NM_016383.5	ENSP00000360988.3		Q9P127-1
LUZP4	ENST00000371921.5 link	c.218G>A	p.Arg73Gln	missense_variant	Exon 2 of 3	2		ENSP00000360989.1		Q5JX98

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111891

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34085

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

156575

Hom.:

AF XY:

0.0000612

AC XY:

AN XY:

49051

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:

0.0000706

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000933

AC:

AN:

1071532

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

345036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000675

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000205

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000842

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111891

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34085

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 23, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.50

DANN

Benign

0.67

DEOGEN2

Benign

0.0012

.;T

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

0.80

N;N

REVEL

Benign

0.029

Sift

Benign

0.49

.;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0010

.;B

Vest4

0.028

MutPred

0.26

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MVP

0.48

MPC

0.021

ClinPred

0.026

GERP RS

-1.3

Varity_R

0.027

gMVP

0.0031

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