Variant X-112779131-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001113490.2(AMOT):c.3023C>T(p.Pro1008Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000918 in 1,089,366 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000092 ( 0 hom. 2 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

Variant links:

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]

AMOT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1632461).

BP6

Variant X-112779131-G-A is Benign according to our data. Variant chrX-112779131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.3023C>T	p.Pro1008Leu	missense_variant	13/14	ENST00000371959.9	NP_001106962.1	Q4VCS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMOT	ENST00000371959.9 link	c.3023C>T	p.Pro1008Leu	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.2327C>T	p.Pro776Leu	missense_variant	10/11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.1796C>T	p.Pro599Leu	missense_variant	11/12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111816

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33988

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

181262

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000251

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.00000921

AC:

AN:

977550

Hom.:

Cov.:

AF XY:

0.00000722

AC XY:

AN XY:

276904

show subpopulations

Gnomad4 AFR exome

AF:

0.0000832

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000194

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000546

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111816

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33988

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000187

Hom.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

AMOT: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.058

T;.;T;T

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.68

T;T;T;.

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.;.;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.076

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Uncertain

0.052

T;D;T;T

Polyphen

0.0020

B;.;.;B

Vest4

0.22

MutPred

0.20

Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);

MVP

0.36

MPC

0.31

ClinPred

0.15

GERP RS

3.3

Varity_R

0.16

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over