chr1-109507777-C-T

Variant names:

• chr1-109507777-C-T
• NM_020703.4:c.1136G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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]

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
AMIGO1	NM_020703.4	c.1136G>A	p.Gly379Asp	missense_variant	Exon 2 of 2	ENST00000369864.5	NP_065754.2
AMIGO1	XM_011541812.3	c.1136G>A	p.Gly379Asp	missense_variant	Exon 2 of 2		XP_011540114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMIGO1	ENST00000369864.5	c.1136G>A	p.Gly379Asp	missense_variant	Exon 2 of 2	1	NM_020703.4	ENSP00000358880.4
AMIGO1	ENST00000369862.1	c.1136G>A	p.Gly379Asp	missense_variant	Exon 2 of 2	5		ENSP00000358878.1

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

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;