Variant X-112778585-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001113490.2(AMOT):c.3237G>A(p.Met1079Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000166 in 1,203,984 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000017 ( 0 hom. 4 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1413553).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.3237G>A	p.Met1079Ile	missense_variant	Exon 14 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.3237G>A	p.Met1079Ile	missense_variant	Exon 14 of 14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.2541G>A	p.Met847Ile	missense_variant	Exon 11 of 11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.2010G>A	p.Met670Ile	missense_variant	Exon 12 of 12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112363

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34523

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

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:

0.0000110

AC:

AN:

181661

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66185

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:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1091621

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

357561

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000955

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112363

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34523

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000939

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

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3237G>A (p.M1079I) alteration is located in exon 11 (coding exon 11) of the AMOT gene. This alteration results from a G to A substitution at nucleotide position 3237, causing the methionine (M) at amino acid position 1079 to be replaced by an isoleucine (I). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

T;.;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

T;T;T;.

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.;.;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.29

N;N;N;N

REVEL

Benign

0.066

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0010

B;.;.;B

Vest4

0.24

MutPred

0.33

Gain of helix (P = 0.062);.;.;Gain of helix (P = 0.062);

MVP

0.34

MPC

0.99

ClinPred

0.52

GERP RS

4.0

Varity_R

0.85

gMVP

0.38

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