NM_032517.6:c.95C>T

Variant names:

• chr10-29291962-C-T
• rs777818463
• NM_032517.6:c.95C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032517.6(LYZL1):​c.95C>T​(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 141,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00011 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: LYZL1 NM_032517.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.207
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10470635).

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.95C>T	p.Ser32Leu	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.95C>T	p.Ser32Leu	missense	Exon 2 of 5	ENSP00000498092.1	Q6UWQ5-1
	LYZL1	ENST00000375500.8	TSL:1	c.233C>T	p.Ser78Leu	missense	Exon 2 of 5	ENSP00000364650.3	Q6UWQ5-2
	LYZL1	ENST00000494304.1	TSL:3	n.38C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000434629.1	H0YDZ2

Frequencies

GnomAD3 genomes AF: 0.0000636 AC: 9 AN: 141544 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000728

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00138

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000157

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 24 AN: 224966 AF XY: 0.000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000155

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000404

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000106 AC: 152 AN: 1436864 Hom.: 3 Cov.: 34 AF XY: 0.000132 AC XY: 94 AN XY: 712968

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

African (AFR) AF: 0.0000301 AC: 1 AN: 33218

American (AMR) AF: 0.000231 AC: 10 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00127 AC: 106 AN: 83500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.0000228 AC: 25 AN: 1095774

Other (OTH) AF: 0.000168 AC: 10 AN: 59420

⚠️ 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 AF: 0.0000635 AC: 9 AN: 141660 Hom.: 0 Cov.: 23 AF XY: 0.0000728 AC XY: 5 AN XY: 68708

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

African (AFR) AF: 0.0000254 AC: 1 AN: 39380

American (AMR) AF: 0.0000727 AC: 1 AN: 13752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3250

East Asian (EAS) AF: 0.00 AC: 0 AN: 4778

South Asian (SAS) AF: 0.00139 AC: 6 AN: 4330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63528

Other (OTH) AF: 0.00 AC: 0 AN: 1886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00458304), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000116 AC: 14

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	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.21
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.096
Sift	Uncertain	0.024	D
Sift4G	Benign	0.10	T
Polyphen		0.011	B
Vest4		0.22
MutPred		0.56		Loss of glycosylation at S78 (P = 0.0503)
MVP		0.35
MPC		1.7
ClinPred		0.050	T
GERP RS		1.3
Varity_R		0.051
gMVP		0.35
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777818463; hg19: chr10-29580891; COSMIC: COSV64966859;