Variant 1-23092083-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000302291.9(LUZP1):c.2179A>G(p.Thr727Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,614,114 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

LUZP1
ENST00000302291.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

LUZP1 (HGNC:14985): (leucine zipper protein 1) This gene encodes a protein that contains a leucine zipper motif. The exact function of the encoded protein is not known. In mice this gene affects neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

LUZP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023269653).

BP6

Variant 1-23092083-T-C is Benign according to our data. Variant chr1-23092083-T-C is described in ClinVar as [Benign]. Clinvar id is 720859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
LUZP1	NM_001142546.4 linkuse as main transcript	c.2179A>G	p.Thr727Ala	missense_variant	4/5	NP_001136018.1	Q86V48-1
LUZP1	NM_001395461.1 linkuse as main transcript	c.2179A>G	p.Thr727Ala	missense_variant	3/4	NP_001382390.1
LUZP1	NM_001395462.2 linkuse as main transcript	c.2179A>G	p.Thr727Ala	missense_variant	3/4	NP_001382391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LUZP1	ENST00000302291.9 linkuse as main transcript	c.2179A>G	p.Thr727Ala	missense_variant	3/4	5		ENSP00000303758.4		Q86V48-1
LUZP1	ENST00000314174.5 linkuse as main transcript	c.2179A>G	p.Thr727Ala	missense_variant	2/3	1		ENSP00000313705.5		Q86V48-2

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

427

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00956

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000769

AC:

193

AN:

250924

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00999

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00908

Gnomad4 AMR exome

AF:

0.000693

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:

0.0000198

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.00280

AC:

427

AN:

152246

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

211

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00953

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.00325

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

DANN

Benign

0.62

DEOGEN2

Benign

0.030

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.20

T;.;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.2

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.26

N;N;N

REVEL

Benign

0.053

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.89

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.025

MVP

0.11

MPC

0.16

ClinPred

0.0064

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.067

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over