X-112779197-G-A

Position:

chrX-112779197-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001113490.2(AMOT):c.2957C>T(p.Pro986Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 768,126 control chromosomes in the GnomAD database, including 4 homozygotes. There are 366 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 35 hem., cov: 23)

Exomes 𝑓: 0.0017 ( 4 hom. 331 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.77

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013519287).

BP6

Variant X-112779197-G-A is Benign according to our data. Variant chrX-112779197-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 789145.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 link	c.2957C>T	p.Pro986Leu	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.2957C>T	p.Pro986Leu	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 link	c.2261C>T	p.Pro754Leu	missense_variant	10/11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 link	c.1730C>T	p.Pro577Leu	missense_variant	11/12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

143

AN:

111875

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

34037

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.00224

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00127

AC:

222

AN:

175067

Hom.:

AF XY:

0.00133

AC XY:

AN XY:

61831

show subpopulations

Gnomad AFR exome

AF:

0.000391

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000484

Gnomad FIN exome

AF:

0.0000640

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.000908

GnomAD4 exome

AF:

0.00174

AC:

1139

AN:

656251

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

331

AN XY:

193191

show subpopulations

Gnomad4 AFR exome

AF:

0.000338

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000529

Gnomad4 FIN exome

AF:

0.0000746

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00128

AC:

143

AN:

111875

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

34037

show subpopulations

Gnomad4 AFR

AF:

0.000293

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00138

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00208

AC:

ExAC

AF:

0.00115

AC:

139

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.2957C>T (p.P986L) 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 2957, causing the proline (P) at amino acid position 986 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.030

T;.;T;T

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.56

T;T;T;.

M_CAP

Benign

0.0067

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.050

N;N;N;N

REVEL

Benign

0.020

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Benign

0.061

T;D;D;T

Polyphen

0.0

B;.;.;B

Vest4

0.068

MVP

0.34

MPC

0.31

ClinPred

0.084

GERP RS

2.0

Varity_R

0.052

gMVP

0.15

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