Genetic Variant LUZP4:p.His158del (chrX-115306328-AATC-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_016383.5(LUZP4):c.472_474delCAT(p.His158del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000658 in 1,209,434 control chromosomes in the GnomAD database, including 1 homozygotes. There are 245 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., 22 hem., cov: 22)

Exomes 𝑓: 0.00067 ( 1 hom. 223 hem. )

Consequence

LUZP4
NM_016383.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0330

Publications

0 publications found

Variant links:

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]

LUZP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_016383.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-115306328-AATC-A is Benign according to our data. Variant chrX-115306328-AATC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661249.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 22 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.472_474delCAT	p.His158del	conservative_inframe_deletion	Exon 4 of 4	NP_057467.1	Q9P127-1
	LUZP4	NM_001318840.2		c.226_228delCAT	p.His76del	conservative_inframe_deletion	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.472_474delCAT	p.His158del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000360988.3	Q9P127-1
	LUZP4	ENST00000371921.5	TSL:2	c.116_118delCAT		3_prime_UTR	Exon 3 of 3	ENSP00000360989.1	Q5JX98

Frequencies

GnomAD3 genomes

AF:

0.000504

AC:

AN:

111193

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000942

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000311

AC:

AN:

183381

AF XY:

0.000265

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000623

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000674

AC:

740

AN:

1098187

Hom.:

AF XY:

0.000613

AC XY:

223

AN XY:

363543

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26402

American (AMR)

AF:

0.0000568

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.000464

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30197

South Asian (SAS)

AF:

0.00

AC:

AN:

54143

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40525

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000848

AC:

714

AN:

842100

Other (OTH)

AF:

0.000239

AC:

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000503

AC:

AN:

111247

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

33429

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30688

American (AMR)

AF:

0.00

AC:

AN:

10376

Ashkenazi Jewish (ASJ)

AF:

0.000377

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3506

South Asian (SAS)

AF:

0.00

AC:

AN:

2610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5921

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000942

AC:

AN:

53089

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000419

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.033

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over