Variant rs138992506 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001113490.2(AMOT):c.3095C>T(p.Ala1032Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,207,493 control chromosomes in the GnomAD database, including 5 homozygotes. There are 109 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., 55 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 3 hom. 54 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.72

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004874915).

BP6

Variant X-112779059-G-A is Benign according to our data. Variant chrX-112779059-G-A is described in ClinVar as [Benign]. Clinvar id is 781558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.3095C>T	p.Ala1032Val	missense_variant	Exon 13 of 14	ENST00000371959.9	NP_001106962.1	Q4VCS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMOT	ENST00000371959.9 link	c.3095C>T	p.Ala1032Val	missense_variant	Exon 13 of 14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.2399C>T	p.Ala800Val	missense_variant	Exon 10 of 11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.1868C>T	p.Ala623Val	missense_variant	Exon 11 of 12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

205

AN:

110118

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

AN XY:

32638

show subpopulations

Gnomad AFR

AF:

0.00631

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000578

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:

0.0000385

Gnomad OTH

AF:

0.00273

GnomAD3 exomes

AF:

0.000495

AC:

AN:

179926

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

65782

show subpopulations

Gnomad AFR exome

AF:

0.00579

Gnomad AMR exome

AF:

0.000477

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

201

AN:

1097322

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

362688

show subpopulations

Gnomad4 AFR exome

AF:

0.00659

Gnomad4 AMR exome

AF:

0.000369

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.00185

AC:

204

AN:

110171

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

AN XY:

32701

show subpopulations

Gnomad4 AFR

AF:

0.00629

Gnomad4 AMR

AF:

0.000481

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000385

Gnomad4 OTH

AF:

0.00270

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.00220

ESP6500AA

AF:

0.00495

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000469

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;.;T;T

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.51

T;T;T;.

M_CAP

Benign

0.0069

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.36

N;N;N;N

REVEL

Benign

0.027

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Uncertain

0.016

D;D;D;D

Polyphen

0.0

B;.;.;B

Vest4

0.16

MVP

0.20

MPC

1.0

ClinPred

0.083

GERP RS

3.3

Varity_R

0.12

gMVP

0.10

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