rs2286064

Positions:

• chrX-112778421-G-C
• chrX-112778421-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113490.2(AMOT):​c.*146C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0958 in 481,997 control chromosomes in the GnomAD database, including 1,711 homozygotes. There are 14,130 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.079 (307 hom., 2733 hem., cov: 23)
  • Exomes 𝑓: 0.10 (1404 hom. 11397 hem.)
• Consequence: AMOT NM_001113490.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.*146C>G		3_prime_UTR_variant	14/14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.*146C>G		3_prime_UTR_variant	14/14	1	NM_001113490.2	ENSP00000361027.3
AMOT	ENST00000304758.5	c.*146C>G		3_prime_UTR_variant	12/12	1		ENSP00000305557.1

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 8793 AN: 111544 Hom.: 305 Cov.: 23 AF XY: 0.0809 AC XY: 2729 AN XY: 33740

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0711

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.0858

GnomAD4 exome AF: 0.101 AC: 37379 AN: 370407 Hom.: 1404 Cov.: 5 AF XY: 0.102 AC XY: 11397 AN XY: 111389

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0681

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0774

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0915

GnomAD4 genome AF: 0.0789 AC: 8802 AN: 111590 Hom.: 307 Cov.: 23 AF XY: 0.0809 AC XY: 2733 AN XY: 33796

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.0969 Hom.: 552

Bravo AF: 0.0746

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.6
DANN	Benign	0.75

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: rs2286064; hg19: chrX-112021649;