8-22148485-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_139278.4(LGI3):c.1322G>A(p.Arg441His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,874 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
LGI3
NM_139278.4 missense
NM_139278.4 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 7.90
Genes affected
LGI3 (HGNC:18711): (leucine rich repeat LGI family member 3) Predicted to enable catalytic activity. Predicted to be involved in regulation of exocytosis. Predicted to be located in extracellular region. Predicted to be active in synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LGI3 | ENST00000306317.7 | c.1322G>A | p.Arg441His | missense_variant | Exon 8 of 8 | 1 | NM_139278.4 | ENSP00000302297.2 | ||
LGI3 | ENST00000424267.6 | c.1250G>A | p.Arg417His | missense_variant | Exon 7 of 7 | 1 | ENSP00000399121.2 | |||
LGI3 | ENST00000520124.5 | n.2765G>A | non_coding_transcript_exon_variant | Exon 6 of 6 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249608Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135116
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GnomAD4 exome AF: 0.0000438 AC: 64AN: 1460642Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 726648
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74432
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects Uncertain:1
Jun 17, 2021
Revvity Omics, Revvity
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0156);.;
MVP
MPC
ClinPred
D
GERP RS
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