rs763897669

Variant names:

• chr8-22148311-C-G
• NM_139278.4:c.1496G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-22148311-C-G
• chr8-22148311-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139278.4(LGI3):​c.1496G>C​(p.Arg499Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R499Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LGI3 NM_139278.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

LGI3 (HGNC:18711): (leucine rich repeat LGI family member 3) Predicted to enable catalytic activity. Predicted to be involved in regulation of exocytosis. Predicted to be located in extracellular region. Predicted to be active in synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22978836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGI3	NM_139278.4	c.1496G>C	p.Arg499Pro	missense_variant	Exon 8 of 8	ENST00000306317.7	NP_644807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGI3	ENST00000306317.7	c.1496G>C	p.Arg499Pro	missense_variant	Exon 8 of 8	1	NM_139278.4	ENSP00000302297.2
LGI3	ENST00000424267.6	c.1424G>C	p.Arg475Pro	missense_variant	Exon 7 of 7	1		ENSP00000399121.2
LGI3	ENST00000520124.5	n.2939G>C		non_coding_transcript_exon_variant	Exon 6 of 6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

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	0.30
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.075	T;T
Polyphen		0.94	P;.
Vest4		0.39
MutPred		0.36		Loss of MoRF binding (P = 0.0936);.;
MVP		0.38
MPC		0.40
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.36
gMVP		0.66

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: chr8-22005824;