1-109507777-C-T

Variant summary

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

The NM_020703.4(AMIGO1):​c.1136G>A​(p.Gly379Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AMIGO1
NM_020703.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39
Variant links:
Genes affected
AMIGO1 (HGNC:20824): (adhesion molecule with Ig like domain 1) Predicted to enable potassium channel regulator activity. Predicted to be involved in several processes, including heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; homophilic cell adhesion via plasma membrane adhesion molecules; and nervous system development. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in dendrite and neuronal cell body membrane. Predicted to be integral component of membrane. Predicted to colocalize with voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
AMIGO1NM_020703.4 linkc.1136G>A p.Gly379Asp missense_variant Exon 2 of 2 ENST00000369864.5 NP_065754.2 Q86WK6
AMIGO1XM_011541812.3 linkc.1136G>A p.Gly379Asp missense_variant Exon 2 of 2 XP_011540114.1 Q86WK6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMIGO1ENST00000369864.5 linkc.1136G>A p.Gly379Asp missense_variant Exon 2 of 2 1 NM_020703.4 ENSP00000358880.4 Q86WK6
AMIGO1ENST00000369862.1 linkc.1136G>A p.Gly379Asp missense_variant Exon 2 of 2 5 ENSP00000358878.1 Q86WK6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Mar 09, 2022
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Gene of Uncertain Clinical Significance -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.88
.;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-4.1
D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
1.0
D;D
Vest4
0.48
MutPred
0.64
Loss of catalytic residue at C380 (P = 0.0961);Loss of catalytic residue at C380 (P = 0.0961);
MVP
0.55
MPC
2.4
ClinPred
0.93
D
GERP RS
6.2
Varity_R
0.49
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr1-110050399; API