rs607230
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_005559.4(LAMA1):c.6004A>T(p.Lys2002Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Failed GnomAD Quality Control
Consequence
LAMA1
NM_005559.4 stop_gained
NM_005559.4 stop_gained
Scores
2
2
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.50
Genes affected
LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA1 | NM_005559.4 | c.6004A>T | p.Lys2002Ter | stop_gained | 42/63 | ENST00000389658.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA1 | ENST00000389658.4 | c.6004A>T | p.Lys2002Ter | stop_gained | 42/63 | 1 | NM_005559.4 | P1 | |
LAMA1 | ENST00000579014.5 | n.7019A>T | non_coding_transcript_exon_variant | 41/62 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152070Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
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GnomAD4 exome Cov.: 25
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Cov.:
25
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152070Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74262
GnomAD4 genome
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Data not reliable, filtered out with message: AC0
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74262
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MutationTaster
Benign
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Vest4
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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