X-115306389-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19495282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP4	NM_016383.5	MANE Select	c.527C>G	p.Ser176Cys	missense	Exon 4 of 4	NP_057467.1	Q9P127-1
	LUZP4	NM_001318840.2		c.281C>G	p.Ser94Cys	missense	Exon 3 of 3	NP_001305769.1	Q9P127-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LUZP4	ENST00000371920.4	TSL:1 MANE Select	c.527C>G	p.Ser176Cys	missense	Exon 4 of 4	ENSP00000360988.3	Q9P127-1
	LUZP4	ENST00000371921.5	TSL:2	c.*171C>G		3_prime_UTR	Exon 3 of 3	ENSP00000360989.1	Q5JX98

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

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841909

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.033
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1344373456; hg19: chrX-114540954;