rs782746537
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP6_Moderate
The NM_001278116.2(L1CAM):c.2065G>A(p.Val689Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,208,747 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000036 ( 0 hom. 0 hem. )
Consequence
L1CAM
NM_001278116.2 missense
NM_001278116.2 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 7.82
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM1
In a domain Fibronectin type-III 1 (size 97) in uniprot entity L1CAM_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_001278116.2
BP6
Variant X-153867428-C-T is Benign according to our data. Variant chrX-153867428-C-T is described in ClinVar as [Benign]. Clinvar id is 569072.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
L1CAM | NM_001278116.2 | c.2065G>A | p.Val689Ile | missense_variant | 17/29 | ENST00000370060.7 | NP_001265045.1 | |
L1CAM | NM_000425.5 | c.2065G>A | p.Val689Ile | missense_variant | 16/28 | NP_000416.1 | ||
L1CAM | NM_024003.3 | c.2065G>A | p.Val689Ile | missense_variant | 16/27 | NP_076493.1 | ||
L1CAM | NM_001143963.2 | c.2050G>A | p.Val684Ile | missense_variant | 15/26 | NP_001137435.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
L1CAM | ENST00000370060.7 | c.2065G>A | p.Val689Ile | missense_variant | 17/29 | 5 | NM_001278116.2 | ENSP00000359077 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000447 AC: 5AN: 111884Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34054
GnomAD3 genomes
AF:
AC:
5
AN:
111884
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
34054
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183517Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67945
GnomAD3 exomes
AF:
AC:
2
AN:
183517
Hom.:
AF XY:
AC XY:
0
AN XY:
67945
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000365 AC: 4AN: 1096863Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 362235
GnomAD4 exome
AF:
AC:
4
AN:
1096863
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
362235
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000447 AC: 5AN: 111884Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34054
GnomAD4 genome
AF:
AC:
5
AN:
111884
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
34054
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
3
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;M;.;M
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0, 1.0
.;D;.;D
Vest4
MutPred
0.82
.;Loss of ubiquitination at K694 (P = 0.0915);.;Loss of ubiquitination at K694 (P = 0.0915);
MVP
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at