rs201151358
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBS1BS2
The NM_001278116.2(L1CAM):c.113C>T(p.Thr38Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,206,671 control chromosomes in the GnomAD database, including 1 homozygotes. There are 220 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., 8 hem., cov: 22)
Exomes 𝑓: 0.00060 ( 1 hom. 212 hem. )
Consequence
L1CAM
NM_001278116.2 missense
NM_001278116.2 missense
Scores
3
8
6
Clinical Significance
Conservation
PhyloP100: 2.50
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 Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.268756).
BP6
Variant X-153872676-G-A is Benign according to our data. Variant chrX-153872676-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153872676-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000602 (659/1095498) while in subpopulation NFE AF= 0.000756 (635/839624). AF 95% confidence interval is 0.000707. There are 1 homozygotes in gnomad4_exome. There are 212 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 8 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
L1CAM | NM_001278116.2 | c.113C>T | p.Thr38Met | missense_variant | 4/29 | ENST00000370060.7 | NP_001265045.1 | |
L1CAM | NM_000425.5 | c.113C>T | p.Thr38Met | missense_variant | 3/28 | NP_000416.1 | ||
L1CAM | NM_024003.3 | c.113C>T | p.Thr38Met | missense_variant | 3/27 | NP_076493.1 | ||
L1CAM | NM_001143963.2 | c.98C>T | p.Thr33Met | missense_variant | 2/26 | NP_001137435.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
L1CAM | ENST00000370060.7 | c.113C>T | p.Thr38Met | missense_variant | 4/29 | 5 | NM_001278116.2 | ENSP00000359077.1 | ||
ENSG00000284987 | ENST00000646191.1 | n.*155C>T | non_coding_transcript_exon_variant | 4/5 | ENSP00000493873.1 | |||||
ENSG00000284987 | ENST00000646191.1 | n.*155C>T | 3_prime_UTR_variant | 4/5 | ENSP00000493873.1 |
Frequencies
GnomAD3 genomes AF: 0.000261 AC: 29AN: 111173Hom.: 0 Cov.: 22 AF XY: 0.000240 AC XY: 8AN XY: 33357
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000251 AC: 46AN: 183381Hom.: 1 AF XY: 0.000251 AC XY: 17AN XY: 67833
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GnomAD4 exome AF: 0.000602 AC: 659AN: 1095498Hom.: 1 Cov.: 30 AF XY: 0.000587 AC XY: 212AN XY: 360902
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GnomAD4 genome AF: 0.000261 AC: 29AN: 111173Hom.: 0 Cov.: 22 AF XY: 0.000240 AC XY: 8AN XY: 33357
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 05, 2021 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 02, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
X-linked hydrocephalus syndrome;C0795953:MASA syndrome;C1839909:X-linked complicated corpus callosum dysgenesis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 06, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 10, 2018 | This variant is associated with the following publications: (PMID: 26891472, 19846429) - |
L1CAM-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 29, 2023 | 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
.;D;.;.;T;T;T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;M;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;.;.;D;.
Polyphen
1.0, 1.0
.;D;.;D;.;.;.;.
Vest4
MVP
MPC
1.5
ClinPred
T
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