rs1800973

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_000239.3(LYZ):c.263C>A(p.Thr88Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 1,613,898 control chromosomes in the GnomAD database, including 2,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 174 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2454 hom. )

Consequence

LYZ
NM_000239.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.85

Publications

37 publications found

Variant links:

Genes affected

LYZ (HGNC:6740): (lysozyme) This gene encodes human lysozyme, whose natural substrate is the bacterial cell wall peptidoglycan (cleaving the beta[1-4]glycosidic linkages between N-acetylmuramic acid and N-acetylglucosamine). Lysozyme is one of the antimicrobial agents found in human milk, and is also present in spleen, lung, kidney, white blood cells, plasma, saliva, and tears. The protein has antibacterial activity against a number of bacterial species. Missense mutations in this gene have been identified in heritable renal amyloidosis. [provided by RefSeq, Oct 2014]

LYZ Gene-Disease associations (from GenCC):

familial visceral amyloidosis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
ALys amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LYZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 5 uncertain in NM_000239.3

BP4

Computational evidence support a benign effect (MetaRNN=0.0052376688).

BP6

Variant 12-69350234-C-A is Benign according to our data. Variant chr12-69350234-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 310331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000239.3. 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
	LYZ	NM_000239.3	MANE Select	c.263C>A	p.Thr88Asn	missense	Exon 2 of 4	NP_000230.1	B2R4C5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYZ	ENST00000261267.7	TSL:1 MANE Select	c.263C>A	p.Thr88Asn	missense	Exon 2 of 4	ENSP00000261267.2	P61626
LYZ	ENST00000549690.1	TSL:2	c.263C>A	p.Thr88Asn	missense	Exon 2 of 3	ENSP00000449898.1	A0A0B4J259
LYZ	ENST00000548839.1	TSL:2	c.263C>A	p.Thr88Asn	missense	Exon 2 of 2	ENSP00000449969.1	F8VV32

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

6398

AN:

152070

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00767

Gnomad FIN

AF:

0.0381

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.0413

GnomAD2 exomes

AF:

0.0422

AC:

10610

AN:

251424

AF XY:

0.0425

show subpopulations

Gnomad AFR exome

AF:

0.00923

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.0742

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0653

Gnomad OTH exome

AF:

0.0479

GnomAD4 exome

AF:

0.0543

AC:

79435

AN:

1461710

Hom.:

2454

Cov.:

AF XY:

0.0538

AC XY:

39085

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.00869

AC:

291

AN:

33480

American (AMR)

AF:

0.0254

AC:

1135

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0719

AC:

1878

AN:

26130

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39682

South Asian (SAS)

AF:

0.00987

AC:

851

AN:

86256

European-Finnish (FIN)

AF:

0.0441

AC:

2355

AN:

53418

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5768

European-Non Finnish (NFE)

AF:

0.0630

AC:

70081

AN:

1111862

Other (OTH)

AF:

0.0451

AC:

2726

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3761

7523

11284

15046

18807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2486

4972

7458

9944

12430

<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:

0.0421

AC:

6400

AN:

152188

Hom.:

174

Cov.:

AF XY:

0.0389

AC XY:

2893

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0108

AC:

449

AN:

41512

American (AMR)

AF:

0.0307

AC:

469

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

254

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00788

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0381

AC:

404

AN:

10594

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0680

AC:

4627

AN:

67998

Other (OTH)

AF:

0.0408

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

317

635

952

1270

1587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0572

Hom.:

1247

Bravo

AF:

0.0406

TwinsUK

AF:

0.0593

AC:

220

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0698

AC:

600

ExAC

AF:

0.0427

AC:

5186

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0643

EpiControl

AF:

0.0644

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial visceral amyloidosis, Ostertag type (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.9

PhyloP100

2.8

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.56

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.057

Polyphen

0.98

Vest4

0.46

MPC

0.87

ClinPred

0.042

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.73

Mutation Taster

=99/1

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over