X-112779087-C-G

Position:

• chrX-112779087-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113490.2(AMOT):​c.3067G>C​(p.Ala1023Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16461119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.3067G>C	p.Ala1023Pro	missense_variant	13/14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.3067G>C	p.Ala1023Pro	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3
AMOT	ENST00000371962.5	c.2371G>C	p.Ala791Pro	missense_variant	10/11	1		ENSP00000361030.1
AMOT	ENST00000304758.5	c.1840G>C	p.Ala614Pro	missense_variant	11/12	1		ENSP00000305557.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2022

The c.3067G>C (p.A1023P) alteration is located in exon 10 (coding exon 10) of the AMOT gene. This alteration results from a G to C substitution at nucleotide position 3067, causing the alanine (A) at amino acid position 1023 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.;T;T
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.51	T;T;T;.
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.16	N;N;N;N
REVEL	Benign	0.099
Sift	Pathogenic	0.0	D;.;D;D
Sift4G	Uncertain	0.027	D;T;D;D
Polyphen		0.95	P;.;.;P
Vest4		0.28
MutPred		0.17		Gain of loop (P = 0.0013);.;.;Gain of loop (P = 0.0013);
MVP		0.46
MPC		0.40
ClinPred		0.61	D
GERP RS		4.0
Varity_R		0.36
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-112022315;