X-112779208-C-A

Variant names:

• chrX-112779208-C-A
• rs200123694
• NM_001113490.2:c.2946G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001113490.2(AMOT):​c.2946G>T​(p.Pro982Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 627,608 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. Synonymous variant affecting the same amino acid position (i.e. P982P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000016 (0 hom. 1 hem.)
• Consequence: AMOT NM_001113490.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.

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.2946G>T	p.Pro982Pro	synonymous	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.2946G>T	p.Pro982Pro	synonymous	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.2946G>T	p.Pro982Pro	synonymous	Exon 13 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.2946G>T	p.Pro982Pro	synonymous	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.2250G>T	p.Pro750Pro	synonymous	Exon 10 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1719G>T	p.Pro573Pro	synonymous	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000159 AC: 1 AN: 627608 Hom.: 0 Cov.: 11 AF XY: 0.00000531 AC XY: 1 AN XY: 188378

African (AFR) AF: 0.00 AC: 0 AN: 17283

American (AMR) AF: 0.00 AC: 0 AN: 34038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16394

East Asian (EAS) AF: 0.00 AC: 0 AN: 27965

South Asian (SAS) AF: 0.00 AC: 0 AN: 44811

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40135

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3076

European-Non Finnish (NFE) AF: 0.00000242 AC: 1 AN: 413357

Other (OTH) AF: 0.00 AC: 0 AN: 30549

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.58
PhyloP100		-2.4

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: rs200123694; hg19: chrX-112022436;