chr9-131009289-C-T

Position:

chr9-131009289-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006059.4(LAMC3):c.75C>T(p.Cys25Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,417,940 control chromosomes in the GnomAD database, including 3,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 1317 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2104 hom. )

Consequence

LAMC3
NM_006059.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 9-131009289-C-T is Benign according to our data. Variant chr9-131009289-C-T is described in ClinVar as [Benign]. Clinvar id is 129472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131009289-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMC3	NM_006059.4 link	c.75C>T	p.Cys25Cys	synonymous_variant	1/28	ENST00000361069.9	NP_006050.3	Q9Y6N6Q8N2D6
LAMC3	XM_011518121.2 link	c.75C>T	p.Cys25Cys	synonymous_variant	1/28		XP_011516423.1
LAMC3	XM_006716921.3 link	c.75C>T	p.Cys25Cys	synonymous_variant	1/23		XP_006716984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMC3	ENST00000361069.9 link	c.75C>T	p.Cys25Cys	synonymous_variant	1/28	2	NM_006059.4	ENSP00000354360.4		Q9Y6N6

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14470

AN:

151508

Hom.:

1312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0247

Gnomad MID

AF:

0.0577

Gnomad NFE

AF:

0.0470

Gnomad OTH

AF:

0.0761

GnomAD3 exomes

AF:

0.0335

AC:

1602

AN:

47810

Hom.:

AF XY:

0.0300

AC XY:

844

AN XY:

28100

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.0327

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00670

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0439

Gnomad OTH exome

AF:

0.0410

GnomAD4 exome

AF:

0.0485

AC:

61406

AN:

1266322

Hom.:

2104

Cov.:

AF XY:

0.0469

AC XY:

29150

AN XY:

621450

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.0411

Gnomad4 ASJ exome

AF:

0.0320

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00688

Gnomad4 FIN exome

AF:

0.0295

Gnomad4 NFE exome

AF:

0.0483

Gnomad4 OTH exome

AF:

0.0559

GnomAD4 genome

AF:

0.0956

AC:

14500

AN:

151618

Hom.:

1317

Cov.:

AF XY:

0.0920

AC XY:

6818

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.0627

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.0247

Gnomad4 NFE

AF:

0.0470

Gnomad4 OTH

AF:

0.0753

Alfa

AF:

0.0573

Hom.:

316

Bravo

AF:

0.104

Asia WGS

AF:

0.0180

AC:

AN:

3436

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 14, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

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