Variant 10-29291895-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032517.6(LYZL1):c.28A>G(p.Ile10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,592,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

LYZL1
NM_032517.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.354

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055947125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZL1	NM_032517.6 link	c.28A>G	p.Ile10Val	missense_variant	2/5	ENST00000649382.2	NP_115906.4	Q6UWQ5-1A0A080YUZ8
LYZL1	XM_005252627.4 link	c.166A>G	p.Ile56Val	missense_variant	2/5		XP_005252684.1
LYZL1	XM_017016791.2 link	c.166A>G	p.Ile56Val	missense_variant	2/5		XP_016872280.1
LYZL1	XR_428650.2 link	n.214A>G		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYZL1	ENST00000649382.2 link	c.28A>G	p.Ile10Val	missense_variant	2/5		NM_032517.6	ENSP00000498092.1	Q6UWQ5-1
LYZL1	ENST00000375500.8 link	c.166A>G	p.Ile56Val	missense_variant	2/5	1		ENSP00000364650.3	Q6UWQ5-2
LYZL1	ENST00000494304.1 link	n.-30A>G		upstream_gene_variant		3		ENSP00000434629.1	H0YDZ2

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000217

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

234460

Hom.:

AF XY:

0.0000396

AC XY:

AN XY:

126352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.0000487

Gnomad NFE exome

AF:

0.00000955

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000471

AC:

AN:

1443570

Hom.:

Cov.:

AF XY:

0.0000572

AC XY:

AN XY:

716434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148494

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000218

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000248

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

Aug 02, 2024

The c.166A>G (p.I56V) alteration is located in exon 2 (coding exon 2) of the LYZL1 gene. This alteration results from a A to G substitution at nucleotide position 166, causing the isoleucine (I) at amino acid position 56 to be replaced by a valine (V). 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

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.6

DANN

Benign

0.24

DEOGEN2

Benign

0.0096

.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.27

N;.

REVEL

Benign

0.029

Sift

Benign

0.38

T;.

Sift4G

Benign

0.35

T;.

Polyphen

0.0010

B;.

Vest4

0.053

MutPred

0.31

Gain of MoRF binding (P = 0.2247);.;

MVP

0.39

MPC

1.7

ClinPred

0.022

GERP RS

2.1

Varity_R

0.018

gMVP

0.17

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