dbSNP rs761847558: LOX:p.Asn51Lys (chr5-122077833-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002317.7(LOX):c.153C>A(p.Asn51Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,400,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LOX
NM_002317.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 2.19

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.115911305).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002317.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOX	NM_002317.7	MANE Select	c.153C>A	p.Asn51Lys	missense	Exon 1 of 7	NP_002308.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LOX	ENST00000231004.5	TSL:1 MANE Select	c.153C>A	p.Asn51Lys	missense	Exon 1 of 7	ENSP00000231004.4
LOX	ENST00000939087.1		c.153C>A	p.Asn51Lys	missense	Exon 2 of 8	ENSP00000609146.1
LOX	ENST00000639739.2	TSL:5	n.153C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000492324.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000267

AC:

AN:

149748

AF XY:

0.0000242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1400286

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

692552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30954

American (AMR)

AF:

0.0000825

AC:

AN:

36350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24988

East Asian (EAS)

AF:

0.00

AC:

AN:

36142

South Asian (SAS)

AF:

0.00

AC:

AN:

79800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

1086080

Other (OTH)

AF:

0.0000172

AC:

AN:

58266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000273

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.7

PhyloP100

2.2

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.95

Vest4

0.67

MutPred

0.40

Gain of ubiquitination at N51 (P = 0.0185)

MVP

0.58

MPC

1.1

ClinPred

0.90

GERP RS

3.8

PromoterAI

0.086

Neutral

(source)

Varity_R

0.90

gMVP

0.76

Mutation Taster

=43/57

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over