Variant X-115306560-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016383.5(LUZP4):c.698G>A(p.Arg233His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,204,155 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 14 hem. )

Consequence

LUZP4
NM_016383.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.841

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=0.022709578).

BP6

Variant X-115306560-G-A is Benign according to our data. Variant chrX-115306560-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2467783.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUZP4	NM_016383.5 linkuse as main transcript	c.698G>A	p.Arg233His	missense_variant	4/4	ENST00000371920.4	NP_057467.1
LUZP4	NM_001318840.2 linkuse as main transcript	c.452G>A	p.Arg151His	missense_variant	3/3		NP_001305769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP4	ENST00000371920.4 linkuse as main transcript	c.698G>A	p.Arg233His	missense_variant	4/4	1	NM_016383.5	ENSP00000360988	P1	Q9P127-1
LUZP4	ENST00000371921.5 linkuse as main transcript	c.*342G>A		3_prime_UTR_variant	3/3	2		ENSP00000360989

Frequencies

GnomAD3 genomes

AF:

0.000103

AC:

AN:

106908

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

30090

show subpopulations

Gnomad AFR

AF:

0.000345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000100

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000436

AC:

AN:

183313

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67771

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1097202

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

363144

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000924

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000103

AC:

AN:

106953

Hom.:

Cov.:

AF XY:

0.0000995

AC XY:

AN XY:

30145

show subpopulations

Gnomad4 AFR

AF:

0.000344

Gnomad4 AMR

AF:

0.000100

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000238

Hom.:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

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

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0010

DANN

Benign

0.57

DEOGEN2

Benign

0.0017

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.43

M_CAP

Benign

0.062

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.86

REVEL

Benign

0.090

Sift

Benign

0.38

Sift4G

Benign

0.36

Polyphen

0.0010

Vest4

0.020

MVP

0.72

MPC

0.021

ClinPred

0.011

GERP RS

-4.6

Varity_R

0.017

gMVP

0.0054

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