rs17010022

Positions:

• chr2-74536131-C-G
• chr2-74536131-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.28

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]

ACMG classification

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	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	c.1113G>C	p.Leu371=	synonymous_variant	7/14	1	NM_032603.5	P1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3457 AN: 152168 Hom.: 389 Cov.: 32

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

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.: 33 AF XY: 0.0142 AC XY: 10322 AN XY: 727116

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.: 32 AF XY: 0.0254 AC XY: 1894 AN XY: 74444

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.: 9

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

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

Other links and lift over

dbSNP: rs17010022; hg19: chr2-74763258; COSMIC: COSV51206163; COSMIC: COSV51206163;