Variant 10-29289217-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 ENST00000375500.8(LYZL1):c.100A>G(p.Asn34Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,587,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.000095 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

LYZL1
ENST00000375500.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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=0.03959006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZL1	NM_032517.6 link	c.-39A>G		5_prime_UTR_variant	1/5	ENST00000649382.2	NP_115906.4	Q6UWQ5-1A0A080YUZ8
LYZL1	XM_005252627.4 link	c.100A>G	p.Asn34Asp	missense_variant	1/5		XP_005252684.1
LYZL1	XM_017016791.2 link	c.100A>G	p.Asn34Asp	missense_variant	1/5		XP_016872280.1
LYZL1	XR_428650.2 link	n.148A>G		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYZL1	ENST00000375500.8 link	c.100A>G	p.Asn34Asp	missense_variant	1/5	1		ENSP00000364650.3		Q6UWQ5-2
LYZL1	ENST00000649382.2 link	c.-39A>G		5_prime_UTR_variant	1/5		NM_032517.6	ENSP00000498092.1		Q6UWQ5-1

Frequencies

GnomAD3 genomes

AF:

0.0000950

AC:

AN:

147366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000264

AC:

AN:

227526

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

124158

show subpopulations

Gnomad AFR exome

AF:

0.000403

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000556

AC:

AN:

1439944

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716208

show subpopulations

Gnomad4 AFR exome

AF:

0.000243

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000950

AC:

AN:

147366

Hom.:

Cov.:

AF XY:

0.0000558

AC XY:

AN XY:

71684

show subpopulations

Gnomad4 AFR

AF:

0.000352

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

Dec 09, 2024

The c.100A>G (p.N34D) alteration is located in exon 1 (coding exon 1) of the LYZL1 gene. This alteration results from a A to G substitution at nucleotide position 100, causing the asparagine (N) at amino acid position 34 to be replaced by an aspartic acid (D). 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

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.9

DANN

Benign

0.74

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.44

M_CAP

Benign

0.018

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.46

REVEL

Benign

0.040

Sift

Benign

0.19

Sift4G

Benign

0.12

Polyphen

0.0040

Vest4

0.20

MVP

0.51

MPC

0.17

ClinPred

0.012

GERP RS

1.1

gMVP

0.032

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