rs768392343

Variant names:

• chrX-112778630-T-G
• rs768392343
• NM_001113490.2:c.3192A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001113490.2(AMOT):​c.3192A>C​(p.Arg1064Ser) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1064G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.701
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113490.2. 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
	AMOT	NM_001113490.2	MANE Select	c.3192A>C	p.Arg1064Ser	missense	Exon 14 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.3192A>C	p.Arg1064Ser	missense	Exon 15 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.3192A>C	p.Arg1064Ser	missense	Exon 14 of 14	NP_001373928.1	Q4VCS5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOT	ENST00000371959.9	TSL:1 MANE Select	c.3192A>C	p.Arg1064Ser	missense	Exon 14 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.2496A>C	p.Arg832Ser	missense	Exon 11 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1965A>C	p.Arg655Ser	missense	Exon 12 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182576 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000183 AC: 2 AN: 1094382 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 1 AN XY: 359990

African (AFR) AF: 0.00 AC: 0 AN: 26375

American (AMR) AF: 0.00 AC: 0 AN: 35169

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19301

East Asian (EAS) AF: 0.0000663 AC: 2 AN: 30168

South Asian (SAS) AF: 0.00 AC: 0 AN: 53332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40375

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839611

Other (OTH) AF: 0.00 AC: 0 AN: 45933

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.70
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.34		Gain of disorder (P = 0.0597)
MVP		0.95
MPC		1.1
ClinPred		0.63	D
GERP RS		0.86
Varity_R		0.52
gMVP		0.54
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs768392343; hg19: chrX-112021858;