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rs1048661

Variant summary

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

The NM_005576.4(LOXL1):c.422G>A(p.Arg141Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83
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-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

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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=0.15081781).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LOXL1NM_005576.4 linkuse as main transcriptc.422G>A p.Arg141Gln missense_variant 1/7 ENST00000261921.8
LOXL1-AS1NR_040069.1 linkuse as main transcriptn.184+860C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LOXL1ENST00000261921.8 linkuse as main transcriptc.422G>A p.Arg141Gln missense_variant 1/71 NM_005576.4 P1
LOXL1-AS1ENST00000685373.1 linkuse as main transcriptn.198+572C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.95e-7
AC:
1
AN:
1439534
Hom.:
0
Cov.:
39
AF XY:
0.00
AC XY:
0
AN XY:
716566
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:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
Cadd
Uncertain
25
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.093
T
Eigen
Benign
-0.052
Eigen_PC
Benign
0.061
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.79
T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
0.75
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.056
Sift
Benign
0.073
T
Sift4G
Benign
0.50
T
Polyphen
0.28
B
Vest4
0.028
MutPred
0.21
Loss of methylation at R141 (P = 0.0102);
MVP
0.39
ClinPred
0.61
D
GERP RS
4.1
Varity_R
0.22
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1048661; hg19: chr15-74219546; API