chr3-42404049-G-A

Position:

• chr3-42404049-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144634.4(LYZL4):​c.368C>T​(p.Ala123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYZL4 NM_144634.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

LYZL4 (HGNC:28387): (lysozyme like 4) 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. LYZL4 is a member of a family of lysozyme-like genes (Zhang et al., 2005 [PubMed 16014814]).[supplied by OMIM, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYZL4	NM_144634.4	c.368C>T	p.Ala123Val	missense_variant	4/5	ENST00000287748.8
LYZL4	NM_001304386.2	c.368C>T	p.Ala123Val	missense_variant	4/5
LYZL4	XM_011533355.4	c.368C>T	p.Ala123Val	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYZL4	ENST00000287748.8	c.368C>T	p.Ala123Val	missense_variant	4/5	1	NM_144634.4	P1
LYZL4	ENST00000441172.1	c.368C>T	p.Ala123Val	missense_variant	4/5	5		P1
LYZL4	ENST00000470991.1	n.398C>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

May 18, 2023

The c.368C>T (p.A123V) alteration is located in exon 4 (coding exon 3) of the LYZL4 gene. This alteration results from a C to T substitution at nucleotide position 368, causing the alanine (A) at amino acid position 123 to be replaced by a valine (V). 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	Benign	0.24
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.4	M;M
MutationTaster	Benign	0.84	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.24
Sift	Benign	0.30	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.78	P;P
Vest4		0.67
MutPred		0.72		Loss of ubiquitination at K118 (P = 0.1113);Loss of ubiquitination at K118 (P = 0.1113);
MVP		0.59
MPC		0.52
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.069
gMVP		0.88

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: chr3-42445541;