ENST00000375500.8:c.100A>G

Variant names:

• chr10-29289217-A-G
• rs141458099
• ENST00000375500.8:c.100A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000375500.8(LYZL1):​c.100A>G​(p.Asn34Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,587,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000095 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: LYZL1 ENST00000375500.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03959006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375500.8. 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.-39A>G		5_prime_UTR	Exon 1 of 5	NP_115906.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYZL1	ENST00000375500.8	TSL:1	c.100A>G	p.Asn34Asp	missense	Exon 1 of 5	ENSP00000364650.3	Q6UWQ5-2
	LYZL1	ENST00000649382.2	MANE Select	c.-39A>G		5_prime_UTR	Exon 1 of 5	ENSP00000498092.1	Q6UWQ5-1
	ENSG00000305098	ENST00000808501.1		n.238-11616T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000950 AC: 14 AN: 147366 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000264 AC: 6 AN: 227526 AF XY: 0.0000161

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000556 AC: 8 AN: 1439944 Hom.: 0 Cov.: 35 AF XY: 0.00000419 AC XY: 3 AN XY: 716208

African (AFR) AF: 0.000243 AC: 8 AN: 32966

American (AMR) AF: 0.00 AC: 0 AN: 42962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 82268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099874

Other (OTH) AF: 0.00 AC: 0 AN: 59204

GnomAD4 genome AF: 0.0000950 AC: 14 AN: 147366 Hom.: 0 Cov.: 23 AF XY: 0.0000558 AC XY: 4 AN XY: 71684

African (AFR) AF: 0.000352 AC: 14 AN: 39816

American (AMR) AF: 0.00 AC: 0 AN: 14530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4840

South Asian (SAS) AF: 0.00 AC: 0 AN: 4426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67046

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

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	0.091
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.9
DANN	Benign	0.74
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.040
Sift	Benign	0.19	T
Sift4G	Benign	0.12	T
Polyphen		0.0040	B
Vest4		0.20
MVP		0.51
MPC		0.17
ClinPred		0.012	T
GERP RS		1.1
PromoterAI		-0.010	Neutral
gMVP		0.032
Mutation Taster		=98/2	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: rs141458099; hg19: chr10-29578146; COSMIC: COSV64966873; COSMIC: COSV64966873;