Variant NM_005576.4:c.482C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_005576.4(LOXL1):c.482C>T(p.Ser161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000433 in 1,601,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

LOXL1 links:

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

LOXL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008223176).

BP6

Variant 15-73927265-C-T is Benign according to our data. Variant chr15-73927265-C-T is described in ClinVar as [Benign]. Clinvar id is 3040211.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4 link	c.482C>T	p.Ser161Leu	missense_variant	Exon 1 of 7	ENST00000261921.8	NP_005567.2	Q08397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8 link	c.482C>T	p.Ser161Leu	missense_variant	Exon 1 of 7	1	NM_005576.4	ENSP00000261921.7		Q08397

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000641

AC:

146

AN:

227598

Hom.:

AF XY:

0.000494

AC XY:

AN XY:

125570

show subpopulations

Gnomad AFR exome

AF:

0.00838

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000886

GnomAD4 exome

AF:

0.000232

AC:

337

AN:

1449586

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

150

AN XY:

721406

show subpopulations

Gnomad4 AFR exome

AF:

0.00730

Gnomad4 AMR exome

AF:

0.000974

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.000749

GnomAD4 genome

AF:

0.00234

AC:

356

AN:

152246

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00784

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.00279

ESP6500AA

AF:

0.00688

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000678

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LOXL1-related disorder

Benign:1

Sep 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

0.13

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.6

REVEL

Benign

0.096

Sift

Benign

0.25

Sift4G

Benign

0.068

Polyphen

0.78

Vest4

0.40

MVP

0.63

ClinPred

0.054

GERP RS

4.1

Varity_R

0.24

gMVP

0.68

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