dbSNP rs17010022: LOXL3:p.Leu371Leu (chr2-74536131-C-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_032603.5(LOXL3):c.1113G>C(p.Leu371Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,613,850 control chromosomes in the GnomAD database, including 2,773 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 393 hom., cov: 32)

Exomes 𝑓: 0.015 ( 2380 hom. )

Consequence

LOXL3
NM_032603.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.28

Publications

8 publications found

Variant links:

Genes affected

LOXL3 (HGNC:13869): (lysyl oxidase like 3) This gene encodes a lysyl oxidase, which likely functions as an amine oxidase and plays a role in the formation of crosslinks in collagens and elastin. Deletion of the related gene in mouse causes neonatal mortality with cleft palate, spine deformity, and defects in collagen organization. A mutation in this gene was found in a family with Stickler syndrome. [provided by RefSeq, Sep 2016]

LOXL3 Gene-Disease associations (from GenCC):

myopia 28, autosomal recessive
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Stickler syndrome
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOXL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 2-74536131-C-G is Benign according to our data. Variant chr2-74536131-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL3	NM_032603.5 link	c.1113G>C	p.Leu371Leu	synonymous_variant	Exon 7 of 14	ENST00000264094.8	NP_115992.1	P58215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL3	ENST00000264094.8 link	c.1113G>C	p.Leu371Leu	synonymous_variant	Exon 7 of 14	1	NM_032603.5	ENSP00000264094.3		P58215-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3457

AN:

152168

Hom.:

389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0812

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0495

AC:

12431

AN:

251136

AF XY:

0.0429

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.000280

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0148

AC:

21689

AN:

1461564

Hom.:

2380

Cov.:

AF XY:

0.0142

AC XY:

10322

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

33480

American (AMR)

AF:

0.141

AC:

6294

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

26132

East Asian (EAS)

AF:

0.269

AC:

10664

AN:

39700

South Asian (SAS)

AF:

0.0235

AC:

2023

AN:

86254

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

53124

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000723

AC:

804

AN:

1112000

Other (OTH)

AF:

0.0282

AC:

1700

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1096

2192

3288

4384

5480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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

AF:

0.0227

AC:

3464

AN:

152286

Hom.:

393

Cov.:

AF XY:

0.0254

AC XY:

1894

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00532

AC:

221

AN:

41548

American (AMR)

AF:

0.0815

AC:

1247

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.323

AC:

1670

AN:

5176

South Asian (SAS)

AF:

0.0347

AC:

167

AN:

4818

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

68022

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.165

AC:

571

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.0

(source)

DANN

Benign

0.84

PhyloP100

3.3

Mutation Taster

=92/8

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over