Variant rs77706750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032603.5(LOXL3):c.1124G>A(p.Arg375His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,852 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 24 hom., cov: 32)

Exomes 𝑓: 0.019 ( 349 hom. )

Consequence

LOXL3
NM_032603.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.937

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014687121).

BP6

Variant 2-74536120-C-T is Benign according to our data. Variant chr2-74536120-C-T is described in ClinVar as [Benign]. Clinvar id is 262090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-74536120-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2221/152238) while in subpopulation NFE AF= 0.0232 (1577/67998). AF 95% confidence interval is 0.0222. There are 24 homozygotes in gnomad4. There are 1026 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL3	NM_032603.5 link	c.1124G>A	p.Arg375His	missense_variant	7/14	ENST00000264094.8	NP_115992.1	P58215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL3	ENST00000264094.8 link	c.1124G>A	p.Arg375His	missense_variant	7/14	1	NM_032603.5	ENSP00000264094.3		P58215-1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2224

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00512

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0147

AC:

3687

AN:

251176

Hom.:

AF XY:

0.0153

AC XY:

2079

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00449

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.00864

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00510

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0228

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0194

AC:

28340

AN:

1461614

Hom.:

349

Cov.:

AF XY:

0.0192

AC XY:

13969

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00343

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.00731

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00541

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0146

AC:

2221

AN:

152238

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1026

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0141

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0262

AC:

101

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0231

AC:

199

ExAC

AF:

0.0149

AC:

1803

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0252

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.;T;.

Eigen

Benign

0.079

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.85

T;T;D;T

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.98

L;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.067

T;T;D;T

Sift4G

Benign

0.47

T;T;D;T

Polyphen

0.96

D;.;P;D

Vest4

0.082

MPC

1.0

ClinPred

0.014

GERP RS

4.2

Varity_R

0.052

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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