8-22148657-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139278.4(LGI3):​c.1150G>A​(p.Gly384Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,614,014 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 17 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 129 hom. )

Consequence

LGI3
NM_139278.4 missense

Scores

4
14

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.14
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0016196668).
BP6
Variant 8-22148657-C-T is Benign according to our data. Variant chr8-22148657-C-T is described in ClinVar as [Benign]. Clinvar id is 770570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGI3NM_139278.4 linkc.1150G>A p.Gly384Ser missense_variant Exon 8 of 8 ENST00000306317.7 NP_644807.1 Q8N145-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGI3ENST00000306317.7 linkc.1150G>A p.Gly384Ser missense_variant Exon 8 of 8 1 NM_139278.4 ENSP00000302297.2 Q8N145-1
LGI3ENST00000424267.6 linkc.1078G>A p.Gly360Ser missense_variant Exon 7 of 7 1 ENSP00000399121.2 Q8N145-2
LGI3ENST00000520124.5 linkn.2593G>A non_coding_transcript_exon_variant Exon 6 of 6 1

Frequencies

GnomAD3 genomes
AF:
0.00460
AC:
700
AN:
152160
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0388
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.0111
AC:
2796
AN:
251116
Hom.:
108
AF XY:
0.00855
AC XY:
1161
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.00142
Gnomad AMR exome
AF:
0.0780
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00963
GnomAD4 exome
AF:
0.00252
AC:
3690
AN:
1461736
Hom.:
129
Cov.:
32
AF XY:
0.00220
AC XY:
1597
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
Gnomad4 AMR exome
AF:
0.0756
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000429
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000585
Gnomad4 OTH exome
AF:
0.00288
GnomAD4 genome
AF:
0.00463
AC:
705
AN:
152278
Hom.:
17
Cov.:
32
AF XY:
0.00474
AC XY:
353
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00180
Gnomad4 AMR
AF:
0.0391
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.000886
Hom.:
4
Bravo
AF:
0.00943
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00852
AC:
1034
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jul 31, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.93
D;D
MetaRNN
Benign
0.0016
T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
1.4
N;N
REVEL
Benign
0.26
Sift
Uncertain
0.011
D;D
Sift4G
Uncertain
0.052
T;T
Polyphen
0.95
P;.
Vest4
0.18
MPC
0.33
ClinPred
0.034
T
GERP RS
5.1
Varity_R
0.092
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149352514; hg19: chr8-22006170; COSMIC: COSV60444629; COSMIC: COSV60444629; API