rs879253714
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001278116.2(L1CAM):c.3489_3490del(p.Glu1164GlyfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S1163S) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
L1CAM
NM_001278116.2 frameshift
NM_001278116.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.76
Genes affected
L1CAM (HGNC:6470): (L1 cell adhesion molecule) The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 X-153863516-TCA-T is Pathogenic according to our data. Variant chrX-153863516-TCA-T is described in ClinVar as [Pathogenic]. Clinvar id is 9992.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
L1CAM | NM_001278116.2 | c.3489_3490del | p.Glu1164GlyfsTer7 | frameshift_variant | 27/29 | ENST00000370060.7 | |
L1CAM | NM_000425.5 | c.3489_3490del | p.Glu1164GlyfsTer7 | frameshift_variant | 26/28 | ||
L1CAM | NM_001143963.2 | c.3474_3475del | p.Glu1159GlyfsTer7 | frameshift_variant | 25/26 | ||
L1CAM | NM_024003.3 | c.3489_3490del | p.Glu1164GlyfsTer7 | frameshift_variant | 26/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L1CAM | ENST00000370060.7 | c.3489_3490del | p.Glu1164GlyfsTer7 | frameshift_variant | 27/29 | 5 | NM_001278116.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
MASA syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1994 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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