X-112780929-G-T

Variant names:

• chrX-112780929-G-T
• rs2286063
• NM_001113490.2:c.2430C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001113490.2(AMOT):​c.2430C>A​(p.Ile810Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,209,693 control chromosomes in the GnomAD database, including 3,496 homozygotes. There are 31,266 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 0.097 (509 hom., 3290 hem., cov: 23)
  • Exomes 𝑓: 0.073 (2987 hom. 27976 hem.)
• Consequence: AMOT NM_001113490.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 8 publications found

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]

MIR4329 (HGNC:38290): (microRNA 4329) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.2430C>A	p.Ile810Ile	synonymous_variant	Exon 12 of 14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.2430C>A	p.Ile810Ile	synonymous_variant	Exon 12 of 14	1	NM_001113490.2	ENSP00000361027.3

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 10872 AN: 111514 Hom.: 508 Cov.: 23

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0659

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.0756

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0980

GnomAD2 exomes AF: 0.121 AC: 22124 AN: 183368 AF XY: 0.117

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.0622

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.0508

Gnomad OTH exome AF: 0.0974

GnomAD4 exome AF: 0.0725 AC: 79638 AN: 1098131 Hom.: 2987 Cov.: 31 AF XY: 0.0770 AC XY: 27976 AN XY: 363497

African (AFR) AF: 0.146 AC: 3848 AN: 26403

American (AMR) AF: 0.250 AC: 8789 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 1225 AN: 19385

East Asian (EAS) AF: 0.181 AC: 5481 AN: 30206

South Asian (SAS) AF: 0.215 AC: 11621 AN: 54144

European-Finnish (FIN) AF: 0.0788 AC: 3191 AN: 40480

Middle Eastern (MID) AF: 0.0471 AC: 195 AN: 4137

European-Non Finnish (NFE) AF: 0.0493 AC: 41519 AN: 842083

Other (OTH) AF: 0.0818 AC: 3769 AN: 46094

GnomAD4 genome AF: 0.0975 AC: 10873 AN: 111562 Hom.: 509 Cov.: 23 AF XY: 0.0974 AC XY: 3290 AN XY: 33774

African (AFR) AF: 0.140 AC: 4295 AN: 30721

American (AMR) AF: 0.192 AC: 2029 AN: 10547

Ashkenazi Jewish (ASJ) AF: 0.0659 AC: 174 AN: 2641

East Asian (EAS) AF: 0.175 AC: 609 AN: 3486

South Asian (SAS) AF: 0.195 AC: 510 AN: 2610

European-Finnish (FIN) AF: 0.0764 AC: 458 AN: 5991

Middle Eastern (MID) AF: 0.0783 AC: 17 AN: 217

European-Non Finnish (NFE) AF: 0.0496 AC: 2636 AN: 53157

Other (OTH) AF: 0.0961 AC: 145 AN: 1509

Alfa AF: 0.0722 Hom.: 3468

Bravo AF: 0.114

EpiCase AF: 0.0470

EpiControl AF: 0.0460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2286063; hg19: chrX-112024157; COSMIC: COSV59060722; COSMIC: COSV59060722;