rs797044997

Variant names:

• chr10-93793269-GC-G
• rs797044997
• NM_005097.4:c.758delC

GermlineCancer (beta)

Variant summary

Our verdict is Pathogenic.

+10 Pathogenic

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 10 classification points (ACGS-UK Somatic Oncogenicity v2025). O2_Very_StrongO3_Moderate

The NM_005097.4(LGI1):c.758delC (p.Ala253ValfsTer32) variant causes a frameshift change. This is a loss-of-function variant that does not trigger NMD. The gene LGI1 is a tumor suppressor gene (CancerMine: 11 TSG citations). The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGI1 NM_005097.4 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.17
• Publications: 2 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, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, ClinGen
• epilepsy, familial temporal lobe, 1

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

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Pathogenic. The variant received 10 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O2Null variant in tumour suppressor gene		Non-NMD frameshift: ≥20 downstream pathogenic — O2 very strong (+8); Use caution in the presence of multiple transcripts; Gene confirmed as TSG in CancerMine (TSG: 11 citations, oncogene: 0 citations, driver: 0 citations).; Frameshift/stop-gained. NMD predicted: false. LoF mechanism: true. Downstream pathogenic count: 34.
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LGI1 NM_005097.4	MANE Select	c.758delC p.Ala253ValfsTer32	frameshift	Exon 7 of 8	Prot: NP_005088.1 UniProt:
	LGI1 NM_001308276.2		c.614delC p.Ala205ValfsTer32	frameshift	Exon 5 of 6	Prot: NP_001295205.1 UniProt:
	LGI1 NM_001308275.2		c.758delC p.Ala253ValfsTer29	frameshift	Exon 7 of 8	Prot: NP_001295204.1 UniProt:

LGI1 NM_005097.4

MANE Select

HGVSc / HGVSpc.758delCp.Ala253ValfsTer32

Exon rankExon 7 of 8

frameshift

Prot: NP_005088.1UniProt: A0A0S2Z4S7O95970-1

LGI1 NM_001308276.2

HGVSc / HGVSpc.614delCp.Ala205ValfsTer32

Exon rankExon 5 of 6

frameshift

Prot: NP_001295205.1UniProt: O95970-3

LGI1 NM_001308275.2

HGVSc / HGVSpc.758delCp.Ala253ValfsTer29

Exon rankExon 7 of 8

frameshift

Prot: NP_001295204.1UniProt: A0A0S2Z4X3O95970-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LGI1 ENST00000371418.9	TSL:1MANE Select	c.758delC p.Ala253ValfsTer32	frameshift	Exon 7 of 8	Prot: ENSP00000360472.4 UniProt:
	LGI1 ENST00000371413.4	TSL:1	c.758delC p.Ala253ValfsTer29	frameshift	Exon 7 of 8	Prot: ENSP00000360467.3 UniProt:
	LGI1 ENST00000627420.2	TSL:1	n.*467delC	3_prime_UTR	Exon 5 of 6	Prot: ENSP00000487116.1 UniProt:

LGI1 ENST00000371418.9

TSL:1MANE Select

HGVSc / HGVSpc.758delCp.Ala253ValfsTer32

Exon rankExon 7 of 8

frameshift

Prot: ENSP00000360472.4UniProt: O95970-1

LGI1 ENST00000371413.4

TSL:1

HGVSc / HGVSpc.758delCp.Ala253ValfsTer29

Exon rankExon 7 of 8

frameshift

Prot: ENSP00000360467.3UniProt: O95970-2

LGI1 ENST00000627420.2

TSL:1

HGVSc / HGVSpn.*467delC

Exon rankExon 5 of 6

3_prime_UTR

Prot: ENSP00000487116.1UniProt: A0A0D9SFS5

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Epilepsy, familial temporal lobe, 1 (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
Mutation Taster	N/A	8/192	disease causing (ClinVar)
PhyloP100	Uncertain	6.2

Showing 2 of 2 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs797044997;

hg19: chr10-95553026;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar