rs146972503

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032603.5(LOXL3):c.79C>G(p.Pro27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,611,874 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P27L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 14 hom. )

Consequence

LOXL3
NM_032603.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.36

Publications

1 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 links:

DOK1 (HGNC:2990): (docking protein 1) The protein encoded by this gene is part of a signal transduction pathway downstream of receptor tyrosine kinases. The encoded protein is a scaffold protein that helps form a platform for the assembly of multiprotein signaling complexes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

DOK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051018).

BP6

Variant 2-74552556-G-C is Benign according to our data. Variant chr2-74552556-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LOXL3	NM_032603.5	MANE Select	c.79C>G	p.Pro27Ala	missense	Exon 2 of 14	NP_115992.1	P58215-1
LOXL3	NM_001289164.3		c.79C>G	p.Pro27Ala	missense	Exon 2 of 12	NP_001276093.1	P58215-3
DOK1	NM_001197260.2		c.-357-2598G>C		intron	N/A	NP_001184189.1	Q99704-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LOXL3	ENST00000264094.8	TSL:1 MANE Select	c.79C>G	p.Pro27Ala	missense	Exon 2 of 14	ENSP00000264094.3	P58215-1
DOK1	ENST00000409429.5	TSL:1	c.-357-2598G>C		intron	N/A	ENSP00000387016.1	Q99704-3
LOXL3	ENST00000946469.1		c.79C>G	p.Pro27Ala	missense	Exon 1 of 13	ENSP00000616528.1

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

348

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00395

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00214

AC:

520

AN:

242750

AF XY:

0.00228

show subpopulations

Gnomad AFR exome

AF:

0.000470

Gnomad AMR exome

AF:

0.000819

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00409

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.000845

GnomAD4 exome

AF:

0.00274

AC:

3992

AN:

1459518

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1985

AN XY:

725904

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

33450

American (AMR)

AF:

0.000898

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00107

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00345

AC:

181

AN:

52516

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00315

AC:

3504

AN:

1111156

Other (OTH)

AF:

0.00234

AC:

141

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

227

455

682

910

1137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.00228

AC:

347

AN:

152356

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41582

American (AMR)

AF:

0.000914

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00395

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00367

AC:

250

AN:

68032

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.00189

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00184

AC:

223

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

-0.063

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

REVEL

Benign

0.067

Sift

Benign

0.21

Sift4G

Benign

0.20

Polyphen

0.13

Vest4

0.25

MVP

0.42

MPC

1.2

ClinPred

0.011

GERP RS

4.8

PromoterAI

0.0056

Neutral

(source)

Varity_R

0.098

gMVP

0.56

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over