Variant chr2-74536131-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032603.5(LOXL3):c.1113G>C(p.Leu371=) 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. In-silico tool predicts a benign outcome for this variant. 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:2

Conservation

PhyloP100: 3.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-74536131-C-G is Benign according to our data. Variant chr2-74536131-C-G is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
LOXL3	NM_032603.5 linkuse as main transcript	c.1113G>C	p.Leu371=	synonymous_variant	7/14	ENST00000264094.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL3	ENST00000264094.8 linkuse as main transcript	c.1113G>C	p.Leu371=	synonymous_variant	7/14	1	NM_032603.5	P1	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

GnomAD3 exomes

AF:

0.0495

AC:

12431

AN:

251136

Hom.:

1541

AF XY:

0.0429

AC XY:

5830

AN XY:

135762

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 SAS exome

AF:

0.0237

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

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.0235

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.000723

Gnomad4 OTH exome

AF:

0.0282

GnomAD4 genome

AF:

0.0227

AC:

3464

AN:

152286

Hom.:

393

Cov.:

AF XY:

0.0254

AC XY:

1894

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00532

Gnomad4 AMR

AF:

0.0815

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.0347

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.0279

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.0

DANN

Benign

0.84

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