NM_005097.4:c.56T>G

Variant names:

• chr10-93758200-T-G
• rs1589746991
• NM_005097.4:c.56T>G

Variant summary

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

The NM_005097.4(LGI1):​c.56T>G​(p.Ile19Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGI1 NM_005097.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.2693677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI1	NM_005097.4	c.56T>G	p.Ile19Ser	missense_variant	Exon 1 of 8	ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.56T>G	p.Ile19Ser	missense_variant	Exon 1 of 8	1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T;.;.;.;.;T;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.94	D;D;.;.;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.29	N;.;.;.;N;.;.;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.19	N;.;.;.;.;.;.;N
REVEL	Uncertain	0.38
Sift	Benign	0.51	T;.;.;.;.;.;.;T
Sift4G	Benign	0.33	T;T;T;T;T;.;T;T
Polyphen		0.043	B;.;.;.;B;.;.;B
Vest4		0.58
MutPred		0.60		Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);Gain of disorder (P = 0.0031);
MVP		0.96
MPC		1.1
ClinPred		0.41	T
GERP RS		4.7
Varity_R		0.19
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;