12-69350170-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP5BP4

The NM_000239.3(LYZ):c.199G>C(p.Asp67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LYZ
NM_000239.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.637

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a disulfide_bond (size 86) in uniprot entity LYSC_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_000239.3

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-69350170-G-C is Pathogenic according to our data. Variant chr12-69350170-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 14375.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.31204122).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYZ	NM_000239.3 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/4	ENST00000261267.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LYZ	ENST00000261267.7 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/4	1	NM_000239.3	P1
LYZ	ENST00000549690.1 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/3	2
LYZ	ENST00000548839.1 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMYLOIDOSIS, HEREDITARY SYSTEMIC 5

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.30

T;.;.

Eigen

Benign

-0.042

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

3.9

H;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.026

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.32

MutPred

0.43

Gain of catalytic residue at R68 (P = 0);Gain of catalytic residue at R68 (P = 0);Gain of catalytic residue at R68 (P = 0);

MVP

0.91

MPC

0.95

ClinPred

0.97

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.90

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

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