Variant X-112779270-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000371959.9(AMOT):c.2884T>G(p.Ser962Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000894 in 637,562 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 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 0.000063 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000095 ( 0 hom. 16 hem. )

Consequence

AMOT
ENST00000371959.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.247

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11742869).

BP6

Variant X-112779270-A-C is Benign according to our data. Variant chrX-112779270-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2252666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 linkuse as main transcript	c.2884T>G	p.Ser962Ala	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 linkuse as main transcript	c.2884T>G	p.Ser962Ala	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027	P3	Q4VCS5-1
AMOT	ENST00000371962.5 linkuse as main transcript	c.2188T>G	p.Ser730Ala	missense_variant	10/11	1		ENSP00000361030	A2
AMOT	ENST00000304758.5 linkuse as main transcript	c.1657T>G	p.Ser553Ala	missense_variant	11/12	1		ENSP00000305557	A2	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

111927

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34209

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000530

AC:

AN:

131979

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

42215

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000144

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:

0.0000745

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000951

AC:

AN:

525635

Hom.:

Cov.:

AF XY:

0.0000960

AC XY:

AN XY:

166653

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000625

AC:

AN:

111927

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34209

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000818

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000441

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.36

DEOGEN2

Benign

0.023

T;.;T;T

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.086

T;T;T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.050

N;N;N;N

REVEL

Benign

0.037

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.16

MVP

0.20

MPC

0.26

ClinPred

0.050

GERP RS

-9.0

Varity_R

0.17

gMVP

0.029

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