1-209615395-T-TC
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_000228.3(LAMB3):c.3394dupG(p.Glu1132GlyfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
LAMB3
NM_000228.3 frameshift
NM_000228.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.84
Publications
2 publications found
Genes affected
LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
LAMB3 Gene-Disease associations (from GenCC):
- junctional epidermolysis bullosaInheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
- junctional epidermolysis bullosa Herlitz typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Laboratory for Molecular Medicine
- junctional epidermolysis bullosa, non-Herlitz typeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Ambry Genetics
- amelogenesis imperfecta type 1AInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- amelogenesis imperfecta type 1Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- generalized junctional epidermolysis bullosa non-Herlitz typeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-209615395-T-TC is Pathogenic according to our data. Variant chr1-209615395-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 180677.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LAMB3 | NM_000228.3 | c.3394dupG | p.Glu1132GlyfsTer28 | frameshift_variant | Exon 23 of 23 | ENST00000356082.9 | NP_000219.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LAMB3 | ENST00000356082.9 | c.3394dupG | p.Glu1132GlyfsTer28 | frameshift_variant | Exon 23 of 23 | 1 | NM_000228.3 | ENSP00000348384.3 | ||
| LAMB3 | ENST00000367030.7 | c.3394dupG | p.Glu1132GlyfsTer28 | frameshift_variant | Exon 23 of 23 | 1 | ENSP00000355997.3 | |||
| LAMB3 | ENST00000391911.5 | c.3394dupG | p.Glu1132GlyfsTer28 | frameshift_variant | Exon 22 of 22 | 1 | ENSP00000375778.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1450072Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 719902 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1450072
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
719902
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33270
American (AMR)
AF:
AC:
0
AN:
44258
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25670
East Asian (EAS)
AF:
AC:
0
AN:
39374
South Asian (SAS)
AF:
AC:
0
AN:
85608
European-Finnish (FIN)
AF:
AC:
0
AN:
52074
Middle Eastern (MID)
AF:
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1104312
Other (OTH)
AF:
AC:
0
AN:
59792
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Amelogenesis imperfecta type 1A Pathogenic:1
Jan 01, 2014
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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