chrX-115306400-C-G

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

17

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]

Genome browser will be placed here

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
LUZP4NM_016383.5 linkc.538C>G p.Leu180Val missense_variant Exon 4 of 4 ENST00000371920.4 NP_057467.1 Q9P127-1
LUZP4NM_001318840.2 linkc.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
LUZP4ENST00000371920.4 linkc.538C>G p.Leu180Val missense_variant Exon 4 of 4 1 NM_016383.5 ENSP00000360988.3 Q9P127-1
LUZP4ENST00000371921.5 linkc.*182C>G 3_prime_UTR_variant Exon 3 of 3 2 ENSP00000360989.1 Q5JX98

Frequencies

GnomAD3 genomes
AF:
0.00000899
AC:
1
AN:
111245
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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:
3
AN:
1097930
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
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:
1
AN:
111245
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
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
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.0070
DANN
Benign
0.72
DEOGEN2
Benign
0.010
T
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
0.34
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.63
N
REVEL
Benign
0.24
Sift
Benign
0.45
T
Sift4G
Benign
0.29
T
Polyphen
0.83
P
Vest4
0.056
MutPred
0.23
Gain of loop (P = 0.0195);
MVP
0.59
MPC
0.030
ClinPred
0.14
T
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.

Other links and lift over

dbSNP: rs1230210795; hg19: chrX-114540965; API