1-109507594-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020703.4(AMIGO1):​c.1319G>A​(p.Arg440Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

AMIGO1
NM_020703.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17795306).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMIGO1NM_020703.4 linkc.1319G>A p.Arg440Gln missense_variant Exon 2 of 2 ENST00000369864.5 NP_065754.2 Q86WK6
AMIGO1XM_011541812.3 linkc.1319G>A p.Arg440Gln 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.1319G>A p.Arg440Gln missense_variant Exon 2 of 2 1 NM_020703.4 ENSP00000358880.4 Q86WK6
AMIGO1ENST00000369862.1 linkc.1319G>A p.Arg440Gln missense_variant Exon 2 of 2 5 ENSP00000358878.1 Q86WK6

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251348
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1319G>A (p.R440Q) alteration is located in exon 2 (coding exon 1) of the AMIGO1 gene. This alteration results from a G to A substitution at nucleotide position 1319, causing the arginine (R) at amino acid position 440 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.057
T;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.85
.;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.14
Sift
Uncertain
0.023
D;D
Sift4G
Benign
0.13
T;T
Polyphen
0.96
D;D
Vest4
0.32
MutPred
0.47
Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP
0.52
MPC
1.7
ClinPred
0.25
T
GERP RS
6.2
Varity_R
0.11
gMVP
0.095

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

LitVar

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

Other links and lift over

dbSNP: rs759291273; hg19: chr1-110050216; API