5-122075482-T-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_002317.7(LOX):c.800A>C(p.Gln267Pro) variant causes a missense 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
LOX
NM_002317.7 missense
NM_002317.7 missense
Scores
9
6
3
Clinical Significance
Conservation
PhyloP100: 5.95
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]
SRFBP1 (HGNC:26333): (serum response factor binding protein 1) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA. Predicted to be located in perinuclear region of cytoplasm. Predicted to be part of 90S preribosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a chain Protein-lysine 6-oxidase, long form (size 248) in uniprot entity LYOX_HUMAN there are 9 pathogenic changes around while only 3 benign (75%) in NM_002317.7
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.88
PP5
Variant 5-122075482-T-G is Pathogenic according to our data. Variant chr5-122075482-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 267293.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOX | NM_002317.7 | c.800A>C | p.Gln267Pro | missense_variant | 3/7 | ENST00000231004.5 | |
LOX | NM_001178102.2 | c.110A>C | p.Gln37Pro | missense_variant | 2/6 | ||
LOX | NM_001317073.1 | c.-92A>C | 5_prime_UTR_variant | 2/6 | |||
SRFBP1 | XM_017009111.3 | c.*157T>G | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOX | ENST00000231004.5 | c.800A>C | p.Gln267Pro | missense_variant | 3/7 | 1 | NM_002317.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Aortic aneurysm, familial thoracic 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 24, 2016 | - - |
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
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at P266 (P = 0.0133);Gain of catalytic residue at P266 (P = 0.0133);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at