dbSNP rs41429348: LOXL1:p.Asp292Glu (chr15-73927659-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005576.4(LOXL1):c.876C>A(p.Asp292Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,335,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D292D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.807

Publications

9 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1701628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4 link	c.876C>A	p.Asp292Glu	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.876C>A	p.Asp292Glu	missense_variant	Exon 1 of 7	1	NM_005576.4	ENSP00000261921.7		Q08397

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

83938

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.00000150

AC:

AN:

1335428

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

658588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27120

American (AMR)

AF:

0.00

AC:

AN:

28714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23686

East Asian (EAS)

AF:

0.00

AC:

AN:

29294

South Asian (SAS)

AF:

0.00

AC:

AN:

74228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33356

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

9.45e-7

AC:

AN:

1057932

Other (OTH)

AF:

0.00

AC:

AN:

55702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.0

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.084

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

-0.81

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.49

REVEL

Benign

0.049

Sift

Benign

0.095

Sift4G

Benign

0.59

Polyphen

0.97

Vest4

0.057

MutPred

0.15

Gain of solvent accessibility (P = 0.0306);

MVP

0.41

ClinPred

0.19

GERP RS

0.55

Varity_R

0.060

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

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

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rs41429348

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over