Variant X-112779357-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001113490.2(AMOT):c.2797G>A(p.Ala933Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 905,807 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000028 ( 0 hom. 9 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.330

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=0.05893904).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.2797G>A	p.Ala933Thr	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.2797G>A	p.Ala933Thr	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.2101G>A	p.Ala701Thr	missense_variant	10/11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.1570G>A	p.Ala524Thr	missense_variant	11/12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

112007

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34205

show subpopulations

Gnomad AFR

AF:

0.0000649

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

114847

Hom.:

AF XY:

0.0000251

AC XY:

AN XY:

39819

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000277

AC:

AN:

793800

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

221368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000384

Gnomad4 SAS exome

AF:

0.0000223

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000343

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

112007

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34205

show subpopulations

Gnomad4 AFR

AF:

0.0000649

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.2797G>A (p.A933T) alteration is located in exon 10 (coding exon 10) of the AMOT gene. This alteration results from a G to A substitution at nucleotide position 2797, causing the alanine (A) at amino acid position 933 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.2

DANN

Benign

0.61

DEOGEN2

Benign

0.034

T;.;T;T

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.53

T;T;T;.

M_CAP

Benign

0.0052

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.33

N;N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.024

D;.;D;D

Sift4G

Benign

0.18

T;D;T;T

Polyphen

0.0020

B;.;.;B

Vest4

0.15

MutPred

0.29

Gain of glycosylation at A933 (P = 3e-04);.;.;Gain of glycosylation at A933 (P = 3e-04);

MVP

0.21

MPC

0.30

ClinPred

0.037

GERP RS

0.34

Varity_R

0.062

gMVP

0.086

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