15-73927258-T-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005576.4(LOXL1):c.475T>G(p.Ser159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,601,216 control chromosomes in the GnomAD database, including 913 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.045 ( 509 hom., cov: 33)
Exomes 𝑓: 0.0043 ( 404 hom. )
Consequence
LOXL1
NM_005576.4 missense
NM_005576.4 missense
Scores
1
1
16
Clinical Significance
Conservation
PhyloP100: 0.985
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0016031265).
BP6
?
Variant 15-73927258-T-G is Benign according to our data. Variant chr15-73927258-T-G is described in ClinVar as [Benign]. Clinvar id is 3055709.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXL1 | NM_005576.4 | c.475T>G | p.Ser159Ala | missense_variant | 1/7 | ENST00000261921.8 | |
LOXL1-AS1 | NR_040069.1 | n.184+807A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXL1 | ENST00000261921.8 | c.475T>G | p.Ser159Ala | missense_variant | 1/7 | 1 | NM_005576.4 | P1 | |
LOXL1-AS1 | ENST00000685373.1 | n.198+519A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0451 AC: 6861AN: 152084Hom.: 508 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0106 AC: 2413AN: 227168Hom.: 175 AF XY: 0.00763 AC XY: 956AN XY: 125364
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GnomAD4 exome AF: 0.00433 AC: 6269AN: 1449024Hom.: 404 Cov.: 36 AF XY: 0.00365 AC XY: 2632AN XY: 721184
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GnomAD4 genome ? AF: 0.0451 AC: 6870AN: 152192Hom.: 509 Cov.: 33 AF XY: 0.0431 AC XY: 3209AN XY: 74418
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3454
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
LOXL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 2020 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
P
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at