1-209615314-TCACGGATCTGCTC-T

Position:

• chr1-209615314-TCACGGATCTGCTC-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The ENST00000356082.9(LAMB3):​c.3463_3475del​(p.Glu1155ThrfsTer51) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LAMB3 ENST00000356082.9 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• 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/exons	MANE	Protein	UniProt
LAMB3	NM_000228.3	c.3463_3475del	p.Glu1155ThrfsTer51	frameshift_variant	23/23	ENST00000356082.9	NP_000219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMB3	ENST00000356082.9	c.3463_3475del	p.Glu1155ThrfsTer51	frameshift_variant	23/23	1	NM_000228.3	ENSP00000348384	P1
LAMB3	ENST00000367030.7	c.3463_3475del	p.Glu1155ThrfsTer51	frameshift_variant	23/23	1		ENSP00000355997	P1
LAMB3	ENST00000391911.5	c.3463_3475del	p.Glu1155ThrfsTer51	frameshift_variant	22/22	1		ENSP00000375778	P1

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

Submissions by phenotype

Amelogenesis imperfecta Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Dental Genetics Laboratory, Seoul National University School of Dentistry

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209788659;