rs886040966
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002317.7(LOX):c.125G>A(p.Trp42Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LOX
NM_002317.7 stop_gained
NM_002317.7 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 3.96
Genes affected
LOX (HGNC:6664): (lysyl oxidase) This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-122077861-C-T is Pathogenic according to our data. Variant chr5-122077861-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 267292.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOX | NM_002317.7 | c.125G>A | p.Trp42Ter | stop_gained | 1/7 | ENST00000231004.5 | |
SRFBP1 | XM_017009111.3 | c.*2536C>T | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOX | ENST00000231004.5 | c.125G>A | p.Trp42Ter | stop_gained | 1/7 | 1 | NM_002317.7 | P1 | |
LOX | ENST00000639739.2 | c.125G>A | p.Trp42Ter | stop_gained, NMD_transcript_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1387758Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 685912
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
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0
AN:
1387758
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Cov.:
32
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AC XY:
0
AN XY:
685912
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aortic aneurysm, familial thoracic 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 24, 2016 | - - |
Familial thoracic aortic aneurysm and aortic dissection Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University Medical Center Hamburg-Eppendorf | Nov 20, 2018 | Evidence for LOF pathogenicity as a common mechanism of disease is available. - |
Acute aortic dissection;C0345050:Congenital aneurysm of ascending aorta Pathogenic:1
Pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | Jan 12, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
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Calibrated prediction
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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