Variant 10-29292004-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032517.6(LYZL1):c.137A>C(p.Asn46Thr) variant causes a missense, splice region change. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LYZL1
NM_032517.6 missense, splice_region

Scores

Splicing: ADA: 0.2731

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LYZL1	NM_032517.6 linkuse as main transcript	c.137A>C	p.Asn46Thr	missense_variant, splice_region_variant	2/5	ENST00000649382.2	NP_115906.4
LYZL1	XM_005252627.4 linkuse as main transcript	c.275A>C	p.Asn92Thr	missense_variant, splice_region_variant	2/5		XP_005252684.1
LYZL1	XM_017016791.2 linkuse as main transcript	c.275A>C	p.Asn92Thr	missense_variant, splice_region_variant	2/5		XP_016872280.1
LYZL1	XR_428650.2 linkuse as main transcript	n.323A>C		splice_region_variant, non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYZL1	ENST00000649382.2 linkuse as main transcript	c.137A>C	p.Asn46Thr	missense_variant, splice_region_variant	2/5		NM_032517.6	ENSP00000498092	P1	Q6UWQ5-1
LYZL1	ENST00000375500.8 linkuse as main transcript	c.275A>C	p.Asn92Thr	missense_variant, splice_region_variant	2/5	1		ENSP00000364650		Q6UWQ5-2
LYZL1	ENST00000494304.1 linkuse as main transcript	c.80A>C	p.Asn27Thr	missense_variant, splice_region_variant, NMD_transcript_variant	1/5	3		ENSP00000434629

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

126354

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000830

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000400

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000744

AC:

AN:

188102

Hom.:

AF XY:

0.0000494

AC XY:

AN XY:

101196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000635

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000225

AC:

260

AN:

1155872

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

117

AN XY:

578414

show subpopulations

Gnomad4 AFR exome

AF:

0.0000324

Gnomad4 AMR exome

AF:

0.000133

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000214

AC:

AN:

126440

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

61166

show subpopulations

Gnomad4 AFR

AF:

0.0000269

Gnomad4 AMR

AF:

0.0000829

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000358

Gnomad4 NFE

AF:

0.000400

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000293

Hom.:

ExAC

AF:

0.0000513

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 11, 2022

The c.275A>C (p.N92T) alteration is located in exon 2 (coding exon 2) of the LYZL1 gene. This alteration results from a A to C substitution at nucleotide position 275, causing the asparagine (N) at amino acid position 92 to be replaced by a threonine (T). 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

Uncertain

0.52

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.8

D;.

REVEL

Uncertain

0.54

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.013

D;.

Polyphen

1.0

D;.

Vest4

0.70

MutPred

0.76

Loss of sheet (P = 0.1501);.;

MVP

0.87

MPC

0.53

ClinPred

0.71

GERP RS

4.6

Varity_R

0.35

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.27

dbscSNV1_RF

Benign

0.48

SpliceAI score (max)

0.050

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