rs141724499

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_006059.4(LAMC3):c.4092C>T(p.Ser1364Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,614,078 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 39 hom. )

Consequence

LAMC3
NM_006059.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

LAMC3 (HGNC:6494): (laminin subunit gamma 3) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 3. The gamma 3 chain is most similar to the gamma 1 chain, and contains all the 6 domains expected of the gamma chain. It is a component of laminin 12. The gamma 3 chain is broadly expressed in skin, heart, lung, and the reproductive tracts. In skin, it is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. Gamma 3 is also a prominent element of the apical surface of ciliated epithelial cells of lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma 3-containing laminins along ciliated epithelial surfaces suggests that the apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells. [provided by RefSeq, Aug 2011]

LAMC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 9-131085585-C-T is Benign according to our data. Variant chr9-131085585-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195884.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=2, Uncertain_significance=1}. Variant chr9-131085585-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMC3	NM_006059.4 link	c.4092C>T	p.Ser1364Ser	synonymous_variant	Exon 25 of 28	ENST00000361069.9	NP_006050.3	Q9Y6N6Q8N2D6
LAMC3	XM_011518121.2 link	c.4110C>T	p.Ser1370Ser	synonymous_variant	Exon 25 of 28		XP_011516423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMC3	ENST00000361069.9 link	c.4092C>T	p.Ser1364Ser	synonymous_variant	Exon 25 of 28	2	NM_006059.4	ENSP00000354360.4		Q9Y6N6

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

563

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00589

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00360

AC:

905

AN:

251268

Hom.:

AF XY:

0.00386

AC XY:

524

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00496

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00505

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00560

AC:

8187

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

4130

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00533

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.00370

AC:

563

AN:

152284

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00588

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00511

Hom.:

Bravo

AF:

0.00341

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00682

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 05, 2014

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LAMC3: BP4, BP7, BS2 -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

May 15, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LAMC3-related disorder

Benign:1

Apr 29, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.4

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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