1-209615314-TCACGGATCTGCTC-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_ModeratePP5

The NM_000228.3(LAMB3):​c.3463_3475delGAGCAGATCCGTG​(p.Glu1155ThrfsTer51) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

LAMB3
NM_000228.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.82

Publications

2 publications found
Variant links:
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 bullosa
    Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
  • junctional epidermolysis bullosa Herlitz type
    Inheritance: 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 type
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Ambry Genetics
  • amelogenesis imperfecta type 1A
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • amelogenesis imperfecta type 1
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • generalized junctional epidermolysis bullosa non-Herlitz type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 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. Fraction of 0.0159 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PP5
Variant 1-209615314-TCACGGATCTGCTC-T is Pathogenic according to our data. Variant chr1-209615314-TCACGGATCTGCTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 2578329.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMB3NM_000228.3 linkc.3463_3475delGAGCAGATCCGTG p.Glu1155ThrfsTer51 frameshift_variant Exon 23 of 23 ENST00000356082.9 NP_000219.2 Q13751A0A0S2Z3R6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMB3ENST00000356082.9 linkc.3463_3475delGAGCAGATCCGTG p.Glu1155ThrfsTer51 frameshift_variant Exon 23 of 23 1 NM_000228.3 ENSP00000348384.3 Q13751
LAMB3ENST00000367030.7 linkc.3463_3475delGAGCAGATCCGTG p.Glu1155ThrfsTer51 frameshift_variant Exon 23 of 23 1 ENSP00000355997.3 Q13751
LAMB3ENST00000391911.5 linkc.3463_3475delGAGCAGATCCGTG p.Glu1155ThrfsTer51 frameshift_variant Exon 22 of 22 1 ENSP00000375778.1 Q13751

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Amelogenesis imperfecta Pathogenic:1
-
Dental Genetics Laboratory, Seoul National University School of Dentistry
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.8
Mutation Taster
=0/200
disease causing (long InDel)

Splicing

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

Publications

Other links and lift over

hg19: chr1-209788659; API