chr10-93797385-T-C

Variant names:

• chr10-93797385-T-C
• rs1554907787
• NM_005097.4:c.1256T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005097.4(LGI1):​c.1256T>C​(p.Leu419Ser) 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. 15/22 in silico tools predict 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: 33)
• Consequence: LGI1 NM_005097.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

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]

LGI1 Gene-Disease associations (from GenCC):

• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• epilepsy, familial temporal lobe, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1592828).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005097.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	NM_005097.4	MANE Select	c.1256T>C	p.Leu419Ser	missense	Exon 8 of 8	NP_005088.1	O95970-1
	LGI1	NM_001308276.2		c.1112T>C	p.Leu371Ser	missense	Exon 6 of 6	NP_001295205.1	O95970-3
	LGI1	NM_001308275.2		c.839-364T>C		intron	N/A	NP_001295204.1	O95970-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGI1	ENST00000371418.9	TSL:1 MANE Select	c.1256T>C	p.Leu419Ser	missense	Exon 8 of 8	ENSP00000360472.4	O95970-1
	LGI1	ENST00000371413.4	TSL:1	c.839-364T>C		intron	N/A	ENSP00000360467.3	O95970-2
	LGI1	ENST00000626307.1	TSL:1	n.5171T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.26
Sift	Uncertain	0.022	D
Sift4G	Benign	0.075	T
Polyphen		0.021	B
Vest4		0.20
MutPred		0.49		Gain of disorder (P = 0.0101)
MVP		0.28
MPC		0.98
ClinPred		0.30	T
GERP RS		4.0
Varity_R		0.24
gMVP		0.54
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs1554907787; hg19: chr10-95557142;