chr20-62309346-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_005560.6(LAMA5):c.11078C>T(p.Pro3693Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,591,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
LAMA5
NM_005560.6 missense
NM_005560.6 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 3.25
Genes affected
LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09229335).
BP6
?
Variant 20-62309346-G-A is Benign according to our data. Variant chr20-62309346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2061071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA5 | NM_005560.6 | c.11078C>T | p.Pro3693Leu | missense_variant | 80/80 | ENST00000252999.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA5 | ENST00000252999.7 | c.11078C>T | p.Pro3693Leu | missense_variant | 80/80 | 1 | NM_005560.6 | P1 | |
LAMA5 | ENST00000370691.6 | n.2873C>T | non_coding_transcript_exon_variant | 17/17 | 1 | ||||
LAMA5 | ENST00000495695.1 | n.579C>T | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 151968Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000297 AC: 65AN: 218526Hom.: 0 AF XY: 0.000280 AC XY: 34AN XY: 121324
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GnomAD4 exome AF: 0.000216 AC: 311AN: 1439138Hom.: 0 Cov.: 32 AF XY: 0.000235 AC XY: 168AN XY: 715680
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GnomAD4 genome ? AF: 0.000191 AC: 29AN: 151968Hom.: 0 Cov.: 30 AF XY: 0.0000943 AC XY: 7AN XY: 74194
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
LAMA5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 19, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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