Variant chr1-9934778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032368.5(LZIC):c.320G>A(p.Arg107Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LZIC
NM_032368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Variant links:

Genes affected

LZIC (HGNC:17497): (leucine zipper and CTNNBIP1 domain containing) Predicted to enable beta-catenin binding activity. Predicted to be involved in response to ionizing radiation. [provided by Alliance of Genome Resources, Apr 2022]

LZIC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZIC	NM_032368.5 linkuse as main transcript	c.320G>A	p.Arg107Gln	missense_variant	5/8	ENST00000377223.6	NP_115744.2	Q8WZA0-1A0A024R4I7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LZIC	ENST00000377223.6 linkuse as main transcript	c.320G>A	p.Arg107Gln	missense_variant	5/8	1	NM_032368.5	ENSP00000366430.1	Q8WZA0-1
LZIC	ENST00000377213.1 linkuse as main transcript	c.320G>A	p.Arg107Gln	missense_variant	5/8	1		ENSP00000366418.1	Q8WZA0-1
LZIC	ENST00000400903.6 linkuse as main transcript	c.320G>A	p.Arg107Gln	missense_variant	4/7	1		ENSP00000383695.2	Q8WZA0-1
LZIC	ENST00000488540.5 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	2/5	2		ENSP00000468610.1	K7ES95

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

The c.320G>A (p.R107Q) alteration is located in exon 4 (coding exon 3) of the LZIC gene. This alteration results from a G to A substitution at nucleotide position 320, causing the arginine (R) at amino acid position 107 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

.;T;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.;D;.

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.9

.;M;M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.5

.;D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0050

.;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.99

.;D;D;D

Vest4

0.91

MVP

0.72

MPC

0.31

ClinPred

0.97

GERP RS

4.8

Varity_R

0.59

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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