Variant 10-29291962-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032517.6(LYZL1):c.95C>T(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 141,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00011 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

LYZL1
NM_032517.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.10470635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LYZL1	NM_032517.6 linkuse as main transcript	c.95C>T	p.Ser32Leu	missense_variant	2/5	ENST00000649382.2
LYZL1	XM_005252627.4 linkuse as main transcript	c.233C>T	p.Ser78Leu	missense_variant	2/5
LYZL1	XM_017016791.2 linkuse as main transcript	c.233C>T	p.Ser78Leu	missense_variant	2/5
LYZL1	XR_428650.2 linkuse as main transcript	n.281C>T		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.95C>T	p.Ser32Leu	missense_variant	2/5		NM_032517.6	P1	Q6UWQ5-1
LYZL1	ENST00000375500.8 linkuse as main transcript	c.233C>T	p.Ser78Leu	missense_variant	2/5	1			Q6UWQ5-2
LYZL1	ENST00000494304.1 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000636

AC:

AN:

141544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00138

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

224966

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

120812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000404

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000106

AC:

152

AN:

1436864

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

712968

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000228

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.0000635

AC:

AN:

141660

Hom.:

Cov.:

AF XY:

0.0000728

AC XY:

AN XY:

68708

show subpopulations

Gnomad4 AFR

AF:

0.0000254

Gnomad4 AMR

AF:

0.0000727

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00139

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000157

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000116

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

Mar 26, 2024

The c.233C>T (p.S78L) alteration is located in exon 2 (coding exon 2) of the LYZL1 gene. This alteration results from a C to T substitution at nucleotide position 233, causing the serine (S) at amino acid position 78 to be replaced by a leucine (L). 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

Benign

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.096

Sift

Uncertain

0.024

D;.

Sift4G

Benign

0.10

T;.

Polyphen

0.011

B;.

Vest4

0.22

MutPred

0.56

Loss of glycosylation at S78 (P = 0.0503);.;

MVP

0.35

MPC

1.7

ClinPred

0.050

GERP RS

1.3

Varity_R

0.051

gMVP

0.35

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