10-93758200-T-C

Position:

• chr10-93758200-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005097.4(LGI1):​c.56T>C​(p.Ile19Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGI1 NM_005097.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

Genes affected

LGI1 (HGNC:6572): (leucine rich glioma inactivated 1) This gene encodes a member of the secreted leucine-rich repeat (LRR) superfamily and shares homology with members of the SLIT protein family. The encoded protein may regulate the activity of voltage-gated potassium channels and may be involved in neuronal growth regulation and cell survival. This gene is rearranged as a result of translocations in glioblastoma cell lines, and it is frequently down-regulated or rearranged in malignant gliomas. Mutations in this gene result in autosomal dominant lateral temporal epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31794232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI1	NM_005097.4	c.56T>C	p.Ile19Thr	missense_variant	1/8	ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.56T>C	p.Ile19Thr	missense_variant	1/8	1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

Jul 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Benign	0.21	T;.;.;.;.;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.94	D;D;.;.;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.1	L;.;.;.;L;.;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.36	N;.;.;.;.;.;.;N
REVEL	Uncertain	0.35
Sift	Benign	0.46	T;.;.;.;.;.;.;T
Sift4G	Benign	0.51	T;T;T;T;T;.;T;T
Polyphen		0.18	B;.;.;.;B;.;.;P
Vest4		0.52
MutPred		0.57		Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);Loss of stability (P = 0.0161);
MVP		0.92
MPC		1.0
ClinPred		0.52	D
GERP RS		4.7
Varity_R		0.087
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1589746991; hg19: chr10-95517957;