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GeneBe

18-23689780-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198129.4(LAMA3):c.97G>C(p.Gly33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,378,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

LAMA3
NM_198129.4 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.221
Variant links:
Genes affected
LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0626429).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LAMA3NM_198129.4 linkuse as main transcriptc.97G>C p.Gly33Arg missense_variant 1/75 ENST00000313654.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMA3ENST00000313654.14 linkuse as main transcriptc.97G>C p.Gly33Arg missense_variant 1/751 NM_198129.4 P1Q16787-2
LAMA3ENST00000399516.7 linkuse as main transcriptc.97G>C p.Gly33Arg missense_variant 1/741 Q16787-3
LAMA3ENST00000585600.5 linkuse as main transcriptc.97G>C p.Gly33Arg missense_variant 1/131

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000290
AC:
4
AN:
1378316
Hom.:
0
Cov.:
31
AF XY:
0.00000294
AC XY:
2
AN XY:
679572
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000857
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.33e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 15, 2023The c.97G>C (p.G33R) alteration is located in exon 1 (coding exon 1) of the LAMA3 gene. This alteration results from a G to C substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
Cadd
Benign
0.30
Dann
Benign
0.90
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.047
N
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.69
N;N
REVEL
Benign
0.017
Sift
Benign
0.087
T;T
Vest4
0.11
MutPred
0.54
Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP
0.095
MPC
1.9
ClinPred
0.048
T
GERP RS
-7.7
gMVP
0.22

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.

Other links and lift over

dbSNP: rs1363412150; hg19: chr18-21269744; API