Variant chr2-99291389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000308528.9(LYG1):c.181G>A(p.Asp61Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LYG1
ENST00000308528.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

LYG1 (HGNC:27014): (lysozyme g1) Predicted to enable lysozyme activity. Predicted to be involved in defense response to Gram-positive bacterium. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LYG1 links:

ENSG00000241962 (HGNC:):

ENSG00000241962 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYG1	NM_174898.3 linkuse as main transcript	c.181G>A	p.Asp61Asn	missense_variant	5/7	ENST00000308528.9	NP_777558.1	Q8N1E2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYG1	ENST00000308528.9 linkuse as main transcript	c.181G>A	p.Asp61Asn	missense_variant	5/7	1	NM_174898.3	ENSP00000311320.4	Q8N1E2
LYG1	ENST00000409448.1 linkuse as main transcript	c.181G>A	p.Asp61Asn	missense_variant	6/8	1		ENSP00000386923.1	Q8N1E2
ENSG00000241962	ENST00000424491.5 linkuse as main transcript	n.*293-29737C>T		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 03, 2022

The c.181G>A (p.D61N) alteration is located in exon 5 (coding exon 3) of the LYG1 gene. This alteration results from a G to A substitution at nucleotide position 181, causing the aspartic acid (D) at amino acid position 61 to be replaced by an asparagine (N). 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

0.18

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Pathogenic

3.5

H;H

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.98

D;D

Vest4

0.76

MutPred

0.86

Gain of catalytic residue at D61 (P = 0.0267);Gain of catalytic residue at D61 (P = 0.0267);

MVP

0.39

MPC

0.44

ClinPred

0.99

GERP RS

3.8

Varity_R

0.48

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over