rs116422150

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006059.4(LAMC3):c.1792G>A(p.Gly598Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,613,700 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 19 hom. )

Consequence

LAMC3
NM_006059.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.74

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

occipital pachygyria and polymicrogyria
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Illumina, Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LAMC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036583543).

BP6

Variant 9-131052652-G-A is Benign according to our data. Variant chr9-131052652-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00977 (1487/152248) while in subpopulation AFR AF = 0.0264 (1095/41540). AF 95% confidence interval is 0.0251. There are 17 homozygotes in GnomAd4. There are 696 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC3	NM_006059.4	MANE Select	c.1792G>A	p.Gly598Arg	missense	Exon 10 of 28	NP_006050.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMC3	ENST00000361069.9	TSL:2 MANE Select	c.1792G>A	p.Gly598Arg	missense	Exon 10 of 28	ENSP00000354360.4	Q9Y6N6
LAMC3	ENST00000868026.1		c.1792G>A	p.Gly598Arg	missense	Exon 10 of 28	ENSP00000538085.1
LAMC3	ENST00000955224.1		c.1792G>A	p.Gly598Arg	missense	Exon 10 of 28	ENSP00000625283.1

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1488

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00337

AC:

841

AN:

249576

AF XY:

0.00287

show subpopulations

Gnomad AFR exome

AF:

0.0253

Gnomad AMR exome

AF:

0.00626

Gnomad ASJ exome

AF:

0.00469

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00194

AC:

2832

AN:

1461452

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1323

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0276

AC:

923

AN:

33474

American (AMR)

AF:

0.00635

AC:

284

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00394

AC:

103

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000174

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.00751

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00108

AC:

1198

AN:

1111856

Other (OTH)

AF:

0.00441

AC:

266

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00977

AC:

1487

AN:

152248

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0264

AC:

1095

AN:

41540

American (AMR)

AF:

0.0152

AC:

232

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

68000

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00349

AC:

424

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00196

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

LAMC3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.030

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

1.7

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.062

Sift

Benign

0.59

Sift4G

Benign

0.62

Polyphen

0.014

Vest4

0.14

MutPred

0.49

Gain of solvent accessibility (P = 0.0789)

MVP

0.46

MPC

0.19

ClinPred

0.0042

GERP RS

2.4

Varity_R

0.055

gMVP

0.46

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over