rs1332142957

Variant names:

• chr9-131009310-G-A
• rs1332142957
• NM_006059.4:c.96G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-131009310-G-A
• chr9-131009310-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_006059.4(LAMC3):​c.96G>A​(p.Pro32Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,453,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P32P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: LAMC3 NM_006059.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 1 publications found

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, Orphanet, Illumina
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-1.79 with no splicing effect.

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.96G>A	p.Pro32Pro	synonymous	Exon 1 of 28	NP_006050.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMC3	ENST00000361069.9	TSL:2 MANE Select	c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 28	ENSP00000354360.4	Q9Y6N6
	LAMC3	ENST00000868026.1		c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 28	ENSP00000538085.1
	LAMC3	ENST00000955224.1		c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 28	ENSP00000625283.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151770 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000307 AC: 4 AN: 1301502 Hom.: 0 Cov.: 30 AF XY: 0.00000312 AC XY: 2 AN XY: 640508

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25788

American (AMR) AF: 0.00 AC: 0 AN: 23072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21996

East Asian (EAS) AF: 0.00 AC: 0 AN: 28034

South Asian (SAS) AF: 0.0000144 AC: 1 AN: 69626

European-Finnish (FIN) AF: 0.0000596 AC: 2 AN: 33558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 9.60e-7 AC: 1 AN: 1041868

Other (OTH) AF: 0.00 AC: 0 AN: 53714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0310196), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151770 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74128

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000956 AC: 1 AN: 10458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		-1.8
PromoterAI		-0.050	Neutral

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

Other links and lift over

dbSNP: rs1332142957; hg19: chr9-133884697;