rs1057516476
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_198129.4(LAMA3):c.6505delG(p.Val2169CysfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,364 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V2169V) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
LAMA3
NM_198129.4 frameshift
NM_198129.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.39
Publications
0 publications found
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]
LAMA3 Gene-Disease associations (from GenCC):
- junctional epidermolysis bullosaInheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
- laryngo-onycho-cutaneous syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- junctional epidermolysis bullosa Herlitz typeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
- junctional epidermolysis bullosa, non-Herlitz typeInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- 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: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 18-23904582-TG-T is Pathogenic according to our data. Variant chr18-23904582-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 370424.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_198129.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| LAMA3 | MANE Select | c.6505delG | p.Val2169CysfsTer39 | frameshift | Exon 51 of 75 | NP_937762.2 | Q16787-2 | ||
| LAMA3 | MANE Plus Clinical | c.1678delG | p.Val560CysfsTer39 | frameshift | Exon 14 of 38 | NP_000218.3 | |||
| LAMA3 | c.6337delG | p.Val2113CysfsTer39 | frameshift | Exon 50 of 74 | NP_001121189.2 | A0A0A0MSA0 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LAMA3 | TSL:1 MANE Select | c.6505delG | p.Val2169CysfsTer39 | frameshift | Exon 51 of 75 | ENSP00000324532.8 | Q16787-2 | ||
| LAMA3 | TSL:1 MANE Plus Clinical | c.1678delG | p.Val560CysfsTer39 | frameshift | Exon 14 of 38 | ENSP00000269217.5 | Q16787-1 | ||
| LAMA3 | TSL:1 | c.6337delG | p.Val2113CysfsTer39 | frameshift | Exon 50 of 74 | ENSP00000382432.2 | Q16787-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455364Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 723222 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1455364
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
723222
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33410
American (AMR)
AF:
AC:
0
AN:
43886
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25894
East Asian (EAS)
AF:
AC:
0
AN:
39508
South Asian (SAS)
AF:
AC:
0
AN:
84860
European-Finnish (FIN)
AF:
AC:
0
AN:
52906
Middle Eastern (MID)
AF:
AC:
0
AN:
5632
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1109202
Other (OTH)
AF:
AC:
0
AN:
60066
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Junctional epidermolysis bullosa gravis of Herlitz (1)
1
-
-
not provided (1)
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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