10-29292657-A-G

Position:

• chr10-29292657-A-G

Variant summary

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

The NM_032517.6(LYZL1):​c.278A>G​(p.His93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LYZL1 NM_032517.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.188

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]

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=0.2833136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZL1	NM_032517.6	c.278A>G	p.His93Arg	missense_variant	3/5	ENST00000649382.2	NP_115906.4
LYZL1	XM_005252627.4	c.416A>G	p.His139Arg	missense_variant	3/5		XP_005252684.1
LYZL1	XM_017016791.2	c.416A>G	p.His139Arg	missense_variant	3/5		XP_016872280.1
LYZL1	XR_428650.2	n.464A>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYZL1	ENST00000649382.2	c.278A>G	p.His93Arg	missense_variant	3/5		NM_032517.6	ENSP00000498092.1
LYZL1	ENST00000375500.8	c.416A>G	p.His139Arg	missense_variant	3/5	1		ENSP00000364650.3
LYZL1	ENST00000494304.1	n.221A>G		non_coding_transcript_exon_variant	2/5	3		ENSP00000434629.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461734 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jul 10, 2024

The c.416A>G (p.H139R) alteration is located in exon 3 (coding exon 3) of the LYZL1 gene. This alteration results from a A to G substitution at nucleotide position 416, causing the histidine (H) at amino acid position 139 to be replaced by an arginine (R). 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	0.075
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.4
DANN	Benign	0.72
DEOGEN2	Benign	0.0063	.;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.065	.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.060	N;.
REVEL	Benign	0.11
Sift	Benign	0.36	T;.
Sift4G	Benign	0.36	T;.
Polyphen		0.0010	B;.
Vest4		0.13
MutPred		0.48		Gain of MoRF binding (P = 0.0381);.;
MVP		0.36
MPC		0.13
ClinPred		0.096	T
GERP RS		0.87
Varity_R		0.074
gMVP		0.41

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: chr10-29581586;