NM_005097.4:c.1331T>C

Variant names:

• chr10-93797460-T-C
• NM_005097.4:c.1331T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005097.4(LGI1):​c.1331T>C​(p.Val444Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LGI1 NM_005097.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI1	NM_005097.4	c.1331T>C	p.Val444Ala	missense_variant	Exon 8 of 8	ENST00000371418.9	NP_005088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI1	ENST00000371418.9	c.1331T>C	p.Val444Ala	missense_variant	Exon 8 of 8	1	NM_005097.4	ENSP00000360472.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N;.;.
REVEL	Uncertain	0.61
Sift	Benign	0.040	D;.;.
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.39	B;.;P
Vest4		0.46
MutPred		0.81		Loss of sheet (P = 0.0457);.;.;
MVP		0.25
MPC		1.1
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.65
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-95557217;