5-122077513-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002317.7(LOX):c.473G>A(p.Arg158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,690 control chromosomes in the GnomAD database, including 23,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2280 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21456 hom. )

Consequence

LOX
NM_002317.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0900

Variant links:

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]

LOX links:

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]

SRFBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011650324).

BP6

Variant 5-122077513-C-T is Benign according to our data. Variant chr5-122077513-C-T is described in ClinVar as [Benign]. Clinvar id is 14363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-122077513-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOX	NM_002317.7 link	c.473G>A	p.Arg158Gln	missense_variant	Exon 1 of 7	ENST00000231004.5	NP_002308.2	P28300D0PNI2
SRFBP1	XM_017009111.3 link	c.*2188C>T		3_prime_UTR_variant	Exon 8 of 8		XP_016864600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LOX	ENST00000231004.5 link	c.473G>A	p.Arg158Gln	missense_variant	Exon 1 of 7	1	NM_002317.7	ENSP00000231004.4	P28300
LOX	ENST00000639739.2 link	n.473G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000492324.2	A0A7P0SNB0
LOX	ENST00000508067.1 link	n.-41G>A		upstream_gene_variant		4		ENSP00000427538.1	H0YAL3

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25752

AN:

152054

Hom.:

2278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.172

AC:

42767

AN:

248724

Hom.:

3752

AF XY:

0.172

AC XY:

23253

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.170

AC:

248906

AN:

1461518

Hom.:

21456

Cov.:

AF XY:

0.170

AC XY:

123922

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.171

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.169

AC:

25765

AN:

152172

Hom.:

2280

Cov.:

AF XY:

0.166

AC XY:

12327

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.167

Hom.:

4593

Bravo

AF:

0.177

TwinsUK

AF:

0.159

AC:

590

ALSPAC

AF:

0.166

AC:

638

ESP6500AA

AF:

0.178

AC:

784

ESP6500EA

AF:

0.174

AC:

1494

ExAC

AF:

0.170

AC:

20681

Asia WGS

AF:

0.144

AC:

500

AN:

3478

EpiCase

AF:

0.168

EpiControl

AF:

0.172

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28714974, 24502826, 22661479, 19654310, 20929399, 22911823) -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: LOX c.473G>A (p.Arg158Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.17 in 248724 control chromosomes in the gnomAD database, including 3752 homozygotes. The observed variant frequency exceeds the estimated maximal expected allele frequency for a pathogenic variant in LOX causing Aortopathy phenotype (1.7e-06), strongly suggesting that the variant is benign. To our knowledge, no penetrant association or occurrence of c.473G>A in individuals affected with Aortopathy has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Nov 18, 2022

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

LOX POLYMORPHISM

Benign:1

May 01, 1993

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.5

DANN

Benign

0.95

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.46

.;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

0.68

N;.

REVEL

Benign

0.048

Sift

Benign

0.54

T;.

Sift4G

Benign

0.75

T;.

Polyphen

0.0

B;B

Vest4

0.018

MPC

0.62

ClinPred

0.0029

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over