Variant X-112779666-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.2488G>A(p.Gly830Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,190,326 control chromosomes in the GnomAD database, including 1 homozygotes. There are 409 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 24 hem., cov: 22)

Exomes 𝑓: 0.0011 ( 1 hom. 385 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

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=0.013961524).

BS2

High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 linkuse as main transcript	c.2488G>A	p.Gly830Arg	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 linkuse as main transcript	c.2488G>A	p.Gly830Arg	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 linkuse as main transcript	c.1792G>A	p.Gly598Arg	missense_variant	10/11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 linkuse as main transcript	c.1261G>A	p.Gly421Arg	missense_variant	11/12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.000706

AC:

AN:

110540

Hom.:

Cov.:

AF XY:

0.000733

AC XY:

AN XY:

32754

show subpopulations

Gnomad AFR

AF:

0.000231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000392

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000815

AC:

141

AN:

173074

Hom.:

AF XY:

0.00100

AC XY:

AN XY:

58924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000726

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000919

Gnomad OTH exome

AF:

0.000944

GnomAD4 exome

AF:

0.00111

AC:

1197

AN:

1079748

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

385

AN XY:

348424

show subpopulations

Gnomad4 AFR exome

AF:

0.000307

Gnomad4 AMR exome

AF:

0.00194

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000691

Gnomad4 FIN exome

AF:

0.0000499

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.000705

AC:

AN:

110578

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

AN XY:

32802

show subpopulations

Gnomad4 AFR

AF:

0.000231

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000820

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000717

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

Aug 12, 2021

The c.2488G>A (p.G830R) 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 2488, causing the glycine (G) at amino acid position 830 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;.;T;T

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.82

T;T;T;.

M_CAP

Benign

0.0080

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.99

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.14

T;.;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.93

P;.;.;P

Vest4

0.096

MutPred

0.34

Gain of MoRF binding (P = 0.0184);.;.;Gain of MoRF binding (P = 0.0184);

MVP

0.37

MPC

0.37

ClinPred

0.054

GERP RS

4.3

Varity_R

0.13

gMVP

0.057

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