rs201474883
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP6BS2
The NM_001278116.2(L1CAM):c.618C>A(p.Asp206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,209,123 control chromosomes in the GnomAD database, including 1 homozygotes. There are 89 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.00027 ( 1 hom. 88 hem. )
Consequence
L1CAM
NM_001278116.2 missense
NM_001278116.2 missense
Scores
4
8
3
Clinical Significance
Conservation
PhyloP100: 3.49
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 Likely_benign. Variant got -3 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_001278116.2
BP6
?
Variant X-153870866-G-T is Benign according to our data. Variant chrX-153870866-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211342.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
BS2
?
High Hemizygotes in GnomAdExome4 at 88 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
L1CAM | NM_001278116.2 | c.618C>A | p.Asp206Glu | missense_variant | 7/29 | ENST00000370060.7 | |
L1CAM | NM_000425.5 | c.618C>A | p.Asp206Glu | missense_variant | 6/28 | ||
L1CAM | NM_024003.3 | c.618C>A | p.Asp206Glu | missense_variant | 6/27 | ||
L1CAM | NM_001143963.2 | c.603C>A | p.Asp201Glu | missense_variant | 5/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L1CAM | ENST00000370060.7 | c.618C>A | p.Asp206Glu | missense_variant | 7/29 | 5 | NM_001278116.2 | A1 | |
L1CAM | ENST00000361699.8 | c.618C>A | p.Asp206Glu | missense_variant | 6/27 | 1 | P4 | ||
L1CAM | ENST00000361981.7 | c.603C>A | p.Asp201Glu | missense_variant | 5/26 | 1 | A1 | ||
L1CAM | ENST00000370055.5 | c.603C>A | p.Asp201Glu | missense_variant | 6/27 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000628 AC: 7AN: 111515Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33673
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000763 AC: 14AN: 183477Hom.: 0 AF XY: 0.000103 AC XY: 7AN XY: 67925
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GnomAD4 exome AF: 0.000266 AC: 292AN: 1097608Hom.: 1 Cov.: 33 AF XY: 0.000242 AC XY: 88AN XY: 362972
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GnomAD4 genome ? AF: 0.0000628 AC: 7AN: 111515Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33673
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 09, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2016 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0, 0.98
.;D;.;D
Vest4
MutPred
0.70
.;Gain of catalytic residue at D206 (P = 0.045);.;Gain of catalytic residue at D206 (P = 0.045);
MVP
MPC
1.4
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