X-115289845-C-T

Variant names:

• chrX-115289845-C-T
• rs782420401
• NM_016383.5:c.86C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_016383.5(LUZP4):​c.86C>T​(p.Ser29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000592 in 1,183,384 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts 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: 22)
  • Exomes 𝑓: 0.0000056 (0 hom. 2 hem.)
• Consequence: LUZP4 NM_016383.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31607658).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

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.86C>T	p.Ser29Phe	missense	Exon 1 of 4	NP_057467.1	Q9P127-1
	LUZP4	NM_001318840.2		c.-42C>T		5_prime_UTR	Exon 1 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.86C>T	p.Ser29Phe	missense	Exon 1 of 4	ENSP00000360988.3	Q9P127-1
	LUZP4	ENST00000371921.5	TSL:2	c.86C>T	p.Ser29Phe	missense	Exon 1 of 3	ENSP00000360989.1	Q5JX98

Frequencies

GnomAD3 genomes AF: 0.00000899 AC: 1 AN: 111275 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.0000277 AC: 5 AN: 180438 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000249

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000560 AC: 6 AN: 1072109 Hom.: 0 Cov.: 25 AF XY: 0.00000588 AC XY: 2 AN XY: 340243

African (AFR) AF: 0.00 AC: 0 AN: 25914

American (AMR) AF: 0.00 AC: 0 AN: 34989

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19141

East Asian (EAS) AF: 0.0000668 AC: 2 AN: 29962

South Asian (SAS) AF: 0.00 AC: 0 AN: 53135

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40173

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.00000488 AC: 4 AN: 819588

Other (OTH) AF: 0.00 AC: 0 AN: 45142

GnomAD4 genome AF: 0.00000899 AC: 1 AN: 111275 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33505

African (AFR) AF: 0.00 AC: 0 AN: 30559

American (AMR) AF: 0.00 AC: 0 AN: 10473

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3525

South Asian (SAS) AF: 0.00 AC: 0 AN: 2644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52951

Other (OTH) AF: 0.00 AC: 0 AN: 1487

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.19
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.32		Loss of sheet (P = 7e-04)
MVP		0.96
MPC		0.023
ClinPred		0.48	T
GERP RS		2.5
PromoterAI		0.026	Neutral
Varity_R		0.16
gMVP		0.016
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs782420401; hg19: chrX-114524411;