chrX-115306612-A-T

Position:

• chrX-115306612-A-T

Variant summary

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

The ENST00000371920.4(LUZP4):​c.750A>T​(p.Arg250Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: LUZP4 ENST00000371920.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.739

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=0.08702114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUZP4	NM_016383.5	c.750A>T	p.Arg250Ser	missense_variant	4/4	ENST00000371920.4	NP_057467.1
LUZP4	NM_001318840.2	c.504A>T	p.Arg168Ser	missense_variant	3/3		NP_001305769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP4	ENST00000371920.4	c.750A>T	p.Arg250Ser	missense_variant	4/4	1	NM_016383.5	ENSP00000360988.3
LUZP4	ENST00000371921.5	c.*394A>T		3_prime_UTR_variant	3/3	2		ENSP00000360989.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097274 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363162

Gnomad4 AFR exome AF: 0.0000379

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.750A>T (p.R250S) alteration is located in exon 4 (coding exon 4) of the LUZP4 gene. This alteration results from a A to T substitution at nucleotide position 750, causing the arginine (R) at amino acid position 250 to be replaced by a serine (S). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.9
DANN	Benign	0.92
DEOGEN2	Benign	0.0091	T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.23
Sift	Benign	0.58	T
Sift4G	Benign	0.062	T
Polyphen		0.88	P
Vest4		0.18
MutPred		0.27		Loss of helix (P = 0.0444);
MVP		0.83
MPC		0.071
ClinPred		0.14	T
GERP RS		-0.11
Varity_R		0.24
gMVP		0.019

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: rs782060246; hg19: chrX-114541177;