Variant NM_001113490.2:c.2479C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001113490.2(AMOT):c.2479C>T(p.Leu827Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,184,660 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000027 ( 0 hom. 11 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.2479C>T	p.Leu827Phe	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.2479C>T	p.Leu827Phe	missense_variant	Exon 13 of 14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.1783C>T	p.Leu595Phe	missense_variant	Exon 10 of 11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.1252C>T	p.Leu418Phe	missense_variant	Exon 11 of 12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

110707

Hom.:

Cov.:

AF XY:

0.0000912

AC XY:

AN XY:

32905

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000412

AC:

AN:

169720

Hom.:

AF XY:

0.0000533

AC XY:

AN XY:

56240

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:

0.0000791

Gnomad OTH exome

AF:

0.000241

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1073953

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

343921

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000339

Gnomad4 OTH exome

AF:

0.0000222

GnomAD4 genome

AF:

0.000126

AC:

AN:

110707

Hom.:

Cov.:

AF XY:

0.0000912

AC XY:

AN XY:

32905

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000486

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2479C>T (p.L827F) alteration is located in exon 10 (coding exon 10) of the AMOT gene. This alteration results from a C to T substitution at nucleotide position 2479, causing the leucine (L) at amino acid position 827 to be replaced by a phenylalanine (F). 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

0.22

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;.;T;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;T;T;.

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.;.;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;.;D;D

Sift4G

Uncertain

0.037

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.71

MutPred

0.38

Loss of disorder (P = 0.0906);.;.;Loss of disorder (P = 0.0906);

MVP

0.75

MPC

0.33

ClinPred

0.31

GERP RS

5.3

Varity_R

0.72

gMVP

0.34

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