X-115302093-T-C

Position:

• chrX-115302093-T-C

Variant summary

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

The NM_016383.5(LUZP4):​c.193T>C​(p.Ser65Pro) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: LUZP4 NM_016383.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500

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=0.14271677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LUZP4	NM_016383.5	c.193T>C	p.Ser65Pro	missense_variant	2/4	ENST00000371920.4	NP_057467.1
LUZP4	NM_001318840.2	c.66T>C	p.Asn22=	synonymous_variant	2/3		NP_001305769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP4	ENST00000371920.4	c.193T>C	p.Ser65Pro	missense_variant	2/4	1	NM_016383.5	ENSP00000360988	P1
LUZP4	ENST00000371921.5	c.193T>C	p.Ser65Pro	missense_variant	2/3	2		ENSP00000360989

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 24

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

Aug 31, 2022

The c.193T>C (p.S65P) alteration is located in exon 2 (coding exon 2) of the LUZP4 gene. This alteration results from a T to C substitution at nucleotide position 193, causing the serine (S) at amino acid position 65 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	.;T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.0	D;N
REVEL	Benign	0.036
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.56	.;P
Vest4		0.13
MutPred		0.16		Loss of phosphorylation at S65 (P = 0.0064);Loss of phosphorylation at S65 (P = 0.0064);
MVP		0.86
MPC		0.16
ClinPred		0.76	D
GERP RS		2.0
Varity_R		0.38
gMVP		0.0049

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-114536658;