Genetic Variant LYZL1:p.Ala4Pro (chr10-29289127-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000375500.8(LYZL1):c.10G>C(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,593,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LYZL1
ENST00000375500.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464

Publications

0 publications found

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:

ENSG00000305098 (HGNC:):

ENSG00000305098 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16712183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375500.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYZL1	NM_032517.6	MANE Select	c.-129G>C		5_prime_UTR	Exon 1 of 5	NP_115906.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYZL1	ENST00000375500.8	TSL:1	c.10G>C	p.Ala4Pro	missense	Exon 1 of 5	ENSP00000364650.3	Q6UWQ5-2
LYZL1	ENST00000649382.2	MANE Select	c.-129G>C		5_prime_UTR	Exon 1 of 5	ENSP00000498092.1	Q6UWQ5-1
ENSG00000305098	ENST00000808501.1		n.238-11526C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32762

American (AMR)

AF:

0.00

AC:

AN:

40356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25446

East Asian (EAS)

AF:

0.00

AC:

AN:

39472

South Asian (SAS)

AF:

0.00

AC:

AN:

83686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1101998

Other (OTH)

AF:

0.00

AC:

AN:

59370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.5

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.31

M_CAP

Benign

0.081

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.81

PhyloP100

-0.46

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.020

REVEL

Benign

0.17

Sift

Benign

0.055

Sift4G

Uncertain

0.033

Polyphen

0.96

Vest4

0.24

MutPred

0.13

Gain of glycosylation at A4 (P = 0.0259)

MVP

0.91

MPC

0.36

ClinPred

0.76

GERP RS

-2.8

PromoterAI

-0.017

Neutral

(source)

gMVP

0.085

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over