12-69350234-C-T

Position:

• chr12-69350234-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000239.3(LYZ):​c.263C>T​(p.Thr88Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T88N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYZ NM_000239.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4092105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZ	NM_000239.3	c.263C>T	p.Thr88Ile	missense_variant	2/4	ENST00000261267.7	NP_000230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYZ	ENST00000261267.7	c.263C>T	p.Thr88Ile	missense_variant	2/4	1	NM_000239.3	ENSP00000261267.2
LYZ	ENST00000549690.1	c.263C>T	p.Thr88Ile	missense_variant	2/3	2		ENSP00000449898.1
LYZ	ENST00000548839.1	c.263C>T	p.Thr88Ile	missense_variant	2/2	2		ENSP00000449969.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D;D;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.049	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.80	P;.;.
Vest4		0.29
MutPred		0.69		Gain of catalytic residue at T88 (P = 0.001);Gain of catalytic residue at T88 (P = 0.001);Gain of catalytic residue at T88 (P = 0.001);
MVP		0.91
MPC		0.48
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.75

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

Other links and lift over

dbSNP: rs1800973; hg19: chr12-69744014;