X-115306389-C-G

Variant names:

• chrX-115306389-C-G
• rs1344373456
• NM_016383.5:c.527C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016383.5(LUZP4):​c.527C>G​(p.Ser176Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,987 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: LUZP4 NM_016383.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

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=0.19495282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LUZP4	NM_016383.5	c.527C>G	p.Ser176Cys	missense_variant	Exon 4 of 4	ENST00000371920.4	NP_057467.1
LUZP4	NM_001318840.2	c.281C>G	p.Ser94Cys	missense_variant	Exon 3 of 3		NP_001305769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LUZP4	ENST00000371920.4	c.527C>G	p.Ser176Cys	missense_variant	Exon 4 of 4	1	NM_016383.5	ENSP00000360988.3
LUZP4	ENST00000371921.5	c.*171C>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000360989.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097987 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363349

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: 0.0000554

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.527C>G (p.S176C) 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 527, causing the serine (S) at amino acid position 176 to be replaced by a cysteine (C). 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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.81
MPC		0.16
ClinPred		0.37	T
GERP RS		1.1
Varity_R		0.19
gMVP		0.014

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

Other links and lift over

dbSNP: rs1344373456; hg19: chrX-114540954;