10-30626122-C-A

Position:

• chr10-30626122-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_183058.3(LYZL2):​c.281G>T​(p.Cys94Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYZL2 NM_183058.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03

Genes affected

LYZL2 (HGNC:29613): (lysozyme like 2) Lysozymes (see LYZ; MIM 153450), especially C-type lysozymes, are well-recognized bacteriolytic factors widely distributed in the animal kingdom and play a mainly protective role in host defense. LYZL2 is a member of a family of lysozyme-like genes (Zhang et al., 2005 [PubMed 16014814]).[supplied by OMIM, Apr 2009]

LYZL2 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZL2	NM_183058.3	c.281G>T	p.Cys94Phe	missense_variant	3/5	ENST00000647634.2	NP_898881.3
LYZL2	XM_011519306.3	c.419G>T	p.Cys140Phe	missense_variant	3/4		XP_011517608.1
LYZL2	XM_011519307.3	c.419G>T	p.Cys140Phe	missense_variant	3/4		XP_011517609.1
LYZL2	XR_930469.3	n.467G>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYZL2	ENST00000647634.2	c.281G>T	p.Cys94Phe	missense_variant	3/5		NM_183058.3	ENSP00000497408.1
LYZL2	ENST00000375318.4	c.419G>T	p.Cys140Phe	missense_variant	3/5	1		ENSP00000364467.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2023

The c.419G>T (p.C140F) alteration is located in exon 3 (coding exon 3) of the LYZL2 gene. This alteration results from a G to T substitution at nucleotide position 419, causing the cysteine (C) at amino acid position 140 to be replaced by a phenylalanine (F). 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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.9	H;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-11	.;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	.;D
Vest4		0.94
MutPred		0.95		.;Gain of ubiquitination at K135 (P = 0.1621);
MVP		0.56
MPC		0.79
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.50
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-30915051;