rs1553277846
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000228.3(LAMB3):c.868T>A(p.Cys290Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
LAMB3
NM_000228.3 missense
NM_000228.3 missense
Scores
12
5
1
Clinical Significance
Conservation
PhyloP100: 8.54
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.994
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB3 | NM_000228.3 | c.868T>A | p.Cys290Ser | missense_variant | 9/23 | ENST00000356082.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB3 | ENST00000356082.9 | c.868T>A | p.Cys290Ser | missense_variant | 9/23 | 1 | NM_000228.3 | P1 | |
LAMB3 | ENST00000367030.7 | c.868T>A | p.Cys290Ser | missense_variant | 9/23 | 1 | P1 | ||
LAMB3 | ENST00000391911.5 | c.868T>A | p.Cys290Ser | missense_variant | 8/22 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461864Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727234
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74218
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Junctional epidermolysis bullosa gravis of Herlitz Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 12, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of glycosylation at C290 (P = 0.0386);Gain of glycosylation at C290 (P = 0.0386);Gain of glycosylation at C290 (P = 0.0386);
MVP
MPC
0.59
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at