10-29292001-G-A

Variant names:

• chr10-29292001-G-A
• rs373858466
• NM_032517.6:c.134G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032517.6(LYZL1):​c.134G>A​(p.Gly45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000861 in 1,161,096 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G45V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: LYZL1 NM_032517.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 0 publications found

Genes affected

LYZL1 (HGNC:30502): (lysozyme like 1) Predicted to enable lysozyme activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305098 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032517.6. 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
	LYZL1	NM_032517.6	MANE Select	c.134G>A	p.Gly45Glu	missense	Exon 2 of 5	NP_115906.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYZL1	ENST00000649382.2	MANE Select	c.134G>A	p.Gly45Glu	missense	Exon 2 of 5	ENSP00000498092.1	Q6UWQ5-1
	LYZL1	ENST00000375500.8	TSL:1	c.272G>A	p.Gly91Glu	missense	Exon 2 of 5	ENSP00000364650.3	Q6UWQ5-2
	LYZL1	ENST00000494304.1	TSL:3	n.77G>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000434629.1	H0YDZ2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 8.61e-7 AC: 1 AN: 1161096 Hom.: 0 Cov.: 34 AF XY: 0.00000172 AC XY: 1 AN XY: 581006

African (AFR) AF: 0.00 AC: 0 AN: 30984

American (AMR) AF: 0.00 AC: 0 AN: 37678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21776

East Asian (EAS) AF: 0.00 AC: 0 AN: 37140

South Asian (SAS) AF: 0.00 AC: 0 AN: 76564

European-Finnish (FIN) AF: 0.0000211 AC: 1 AN: 47492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 854620

Other (OTH) AF: 0.00 AC: 0 AN: 50266

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.43
Sift	Benign	0.064	T
Sift4G	Benign	0.15	T
Polyphen		0.85	P
Vest4		0.76
MutPred		0.67		Gain of solvent accessibility (P = 0.0411)
MVP		0.76
MPC		0.23
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.32
gMVP		0.70
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs373858466; hg19: chr10-29580930; COSMIC: COSV64966447;