Variant 10-29291919-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032517.6(LYZL1):c.52G>A(p.Glu18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,590,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LYZL1
NM_032517.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

LYZL1 (HGNC:30502): (lysozyme like 1) Predicted to enable lysozyme activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LYZL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115982145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LYZL1	NM_032517.6 linkuse as main transcript	c.52G>A	p.Glu18Lys	missense_variant	2/5	ENST00000649382.2
LYZL1	XM_005252627.4 linkuse as main transcript	c.190G>A	p.Glu64Lys	missense_variant	2/5
LYZL1	XM_017016791.2 linkuse as main transcript	c.190G>A	p.Glu64Lys	missense_variant	2/5
LYZL1	XR_428650.2 linkuse as main transcript	n.238G>A		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYZL1	ENST00000649382.2 linkuse as main transcript	c.52G>A	p.Glu18Lys	missense_variant	2/5		NM_032517.6	P1	Q6UWQ5-1
LYZL1	ENST00000375500.8 linkuse as main transcript	c.190G>A	p.Glu64Lys	missense_variant	2/5	1			Q6UWQ5-2
LYZL1	ENST00000494304.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000703

AC:

AN:

142302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000422

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000418

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.000532

GnomAD3 exomes

AF:

0.0000925

AC:

AN:

237942

Hom.:

AF XY:

0.0000701

AC XY:

AN XY:

128336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000594

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000242

AC:

AN:

1448626

Hom.:

Cov.:

AF XY:

0.0000250

AC XY:

AN XY:

719372

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000477

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000472

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000544

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000703

AC:

AN:

142302

Hom.:

Cov.:

AF XY:

0.0000720

AC XY:

AN XY:

69464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000422

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000418

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000157

Gnomad4 OTH

AF:

0.000532

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000743

AC:

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

May 06, 2024

The c.190G>A (p.E64K) alteration is located in exon 2 (coding exon 2) of the LYZL1 gene. This alteration results from a G to A substitution at nucleotide position 190, causing the glutamic acid (E) at amino acid position 64 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Pathogenic

2.9

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.23

Sift

Benign

0.069

T;.

Sift4G

Uncertain

0.047

D;.

Polyphen

0.87

P;.

Vest4

0.46

MVP

0.72

MPC

2.1

ClinPred

0.085

GERP RS

1.4

Varity_R

0.069

gMVP

0.37

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