rs2286063

Positions:

• chrX-112780929-G-C
• chrX-112780929-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001113490.2(AMOT):​c.2430C>G​(p.Ile810Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,143 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

Genes affected

AMOT (HGNC:17810): (angiomotin) This gene belongs to the motin family of angiostatin binding proteins characterized by conserved coiled-coil domains and C-terminal PDZ binding motifs. The encoded protein is expressed predominantly in endothelial cells of capillaries as well as larger vessels of the placenta where it may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.2430C>G	p.Ile810Met	missense_variant	12/14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.2430C>G	p.Ile810Met	missense_variant	12/14	1	NM_001113490.2	ENSP00000361027.3
AMOT	ENST00000371962.5	c.1734C>G	p.Ile578Met	missense_variant	9/11	1		ENSP00000361030.1
AMOT	ENST00000304758.5	c.1203C>G	p.Ile401Met	missense_variant	10/12	1		ENSP00000305557.1
AMOT	ENST00000371958.1	c.1734C>G	p.Ile578Met	missense_variant	9/9	5		ENSP00000361026.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098143 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363503

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T;T;T;.;T
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.0	N;.;.;N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.73	N;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D;.;D;D;T
Sift4G	Benign	0.082	T;T;T;T;T
Polyphen		1.0	D;.;.;D;.
Vest4		0.69
MutPred		0.28		Gain of phosphorylation at T806 (P = 0.1196);.;.;Gain of phosphorylation at T806 (P = 0.1196);.;
MVP		0.70
MPC		0.31
ClinPred		0.89	D
GERP RS		3.9
Varity_R		0.46
gMVP		0.31

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

Other links and lift over

dbSNP: rs2286063; hg19: chrX-112024157;