X-112778662-C-T

Variant names:

• chrX-112778662-C-T
• NM_001113490.2:c.3160G>A
• AMOT p.Gly1054Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001113490.2(AMOT):​c.3160G>A​(p.Gly1054Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: AMOT NM_001113490.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34643543).

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.3160G>A	p.Gly1054Arg	missense splice_region	Exon 14 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.3160G>A	p.Gly1054Arg	missense splice_region	Exon 15 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.3160G>A	p.Gly1054Arg	missense splice_region	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.3160G>A	p.Gly1054Arg	missense splice_region	Exon 14 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.2464G>A	p.Gly822Arg	missense splice_region	Exon 11 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1933G>A	p.Gly645Arg	missense splice_region	Exon 12 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.025	D
Varity_R		0.36
gMVP		0.34
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-112021890;