rs781908326

chrX-153872214-C-AchrX-153872214-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001278116.2(L1CAM):c.338G>T(p.Arg113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R113H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: L1CAM NM_001278116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L1CAM	NM_001278116.2	c.338G>T	p.Arg113Leu	missense_variant	5/29	ENST00000370060.7
L1CAM	NM_000425.5	c.338G>T	p.Arg113Leu	missense_variant	4/28
L1CAM	NM_024003.3	c.338G>T	p.Arg113Leu	missense_variant	4/27
L1CAM	NM_001143963.2	c.323G>T	p.Arg108Leu	missense_variant	3/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L1CAM	ENST00000370060.7	c.338G>T	p.Arg113Leu	missense_variant	5/29	5	NM_001278116.2	A1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183388 Hom.: 0 AF XY: 0.0000147 AC XY: 1 AN XY: 67838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097343 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362719

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
Cadd	Pathogenic	26
Dann	Uncertain	1.0
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.92	D;D;.;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	D;D;D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;.;.
Polyphen		1.0, 0.95	.;D;.;P;.;.
Vest4		0.61
MutPred		0.66		.;Loss of MoRF binding (P = 0.0083);.;Loss of MoRF binding (P = 0.0083);Loss of MoRF binding (P = 0.0083);.;
MVP		0.59
MPC		1.7
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.76
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs781908326; hg19: chrX-153137669;