Variant 10-29291858-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032517.6(LYZL1):c.-10G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LYZL1
NM_032517.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0730

Variant links:

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]

LYZL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2624028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYZL1	NM_032517.6 link	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	2/5	ENST00000649382.2	NP_115906.4	Q6UWQ5-1A0A080YUZ8
LYZL1	NM_032517.6 link	c.-10G>T		5_prime_UTR_variant	2/5	ENST00000649382.2	NP_115906.4	Q6UWQ5-1A0A080YUZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYZL1	ENST00000649382.2 link	c.-10G>T		5_prime_UTR_premature_start_codon_gain_variant	2/5		NM_032517.6	ENSP00000498092.1	Q6UWQ5-1
LYZL1	ENST00000375500.8 link	c.129G>T	p.Gln43His	missense_variant	2/5	1		ENSP00000364650.3	Q6UWQ5-2
LYZL1	ENST00000649382.2 link	c.-10G>T		5_prime_UTR_variant	2/5		NM_032517.6	ENSP00000498092.1	Q6UWQ5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000941

AC:

AN:

212628

Hom.:

AF XY:

0.00000882

AC XY:

AN XY:

113432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.07e-7

AC:

AN:

1415426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000833

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.129G>T (p.Q43H) alteration is located in exon 2 (coding exon 2) of the LYZL1 gene. This alteration results from a G to T substitution at nucleotide position 129, causing the glutamine (Q) at amino acid position 43 to be replaced by a histidine (H). 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

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

DANN

Uncertain

0.99

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

M_CAP

Benign

0.058

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.86

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.51

REVEL

Benign

0.11

Sift

Benign

0.11

Sift4G

Benign

0.14

Polyphen

0.92

Vest4

0.33

MutPred

0.44

Gain of methylation at R46 (P = 0.0585);

MVP

0.67

MPC

1.8

ClinPred

0.24

GERP RS

2.4

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over