chr1-109508371-C-T

Variant names:

• chr1-109508371-C-T
• NM_020703.4:c.542G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020703.4(AMIGO1):​c.542G>A​(p.Gly181Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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: 0.00
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061111033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020703.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMIGO1	NM_020703.4	MANE Select	c.542G>A	p.Gly181Glu	missense	Exon 2 of 2	NP_065754.2	Q86WK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMIGO1	ENST00000369864.5	TSL:1 MANE Select	c.542G>A	p.Gly181Glu	missense	Exon 2 of 2	ENSP00000358880.4	Q86WK6
	AMIGO1	ENST00000369862.1	TSL:5	c.542G>A	p.Gly181Glu	missense	Exon 2 of 2	ENSP00000358878.1	Q86WK6
	AMIGO1	ENST00000887776.1		c.542G>A	p.Gly181Glu	missense	Exon 2 of 2	ENSP00000557835.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.084
Sift	Benign	0.18	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.31
MutPred		0.58		Gain of disorder (P = 0.0389)
MVP		0.24
MPC		1.2
ClinPred		0.087	T
GERP RS		4.6
Varity_R		0.057
gMVP		0.85
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr1-110050993; COSMIC: COSV63990601;