chr10-29291874-G-C

Variant names:

• chr10-29291874-G-C
• NM_032517.6:c.7G>C

Variant summary

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

The NM_032517.6(LYZL1):​c.7G>C​(p.Ala3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LYZL1 NM_032517.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.885
• 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.7G>C	p.Ala3Pro	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.7G>C	p.Ala3Pro	missense	Exon 2 of 5	ENSP00000498092.1	Q6UWQ5-1
	LYZL1	ENST00000375500.8	TSL:1	c.145G>C	p.Ala49Pro	missense	Exon 2 of 5	ENSP00000364650.3	Q6UWQ5-2
	ENSG00000305098	ENST00000808501.1		n.238-14273C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.00e-7 AC: 1 AN: 1428232 Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1 AN XY: 707210

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 41684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23648

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 81106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5168

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092996

Other (OTH) AF: 0.00 AC: 0 AN: 59010

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.89
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.58	N
REVEL	Uncertain	0.45
Sift	Benign	0.052	T
Sift4G	Benign	0.23	T
Polyphen		0.96	D
Vest4		0.71
MutPred		0.66		Loss of helix (P = 0.0138)
MVP		0.69
MPC		3.4
ClinPred		0.59	D
GERP RS		2.5
Varity_R		0.13
gMVP		0.48
Mutation Taster		=71/29	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

hg19: chr10-29580803;