X-112779653-G-T

Position:

chrX-112779653-G-T

Variant summary

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

The NM_001113490.2(AMOT):c.2501C>A(p.Ala834Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,201,938 control chromosomes in the GnomAD database, including 1 homozygotes. There are 44 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.00095 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 1 hom. 24 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008574426).

BP6

Variant X-112779653-G-T is Benign according to our data. Variant chrX-112779653-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 715211.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 linkuse as main transcript	c.2501C>A	p.Ala834Asp	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.2501C>A	p.Ala834Asp	missense_variant	13/14	1	NM_001113490.2	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5 linkuse as main transcript	c.1805C>A	p.Ala602Asp	missense_variant	10/11	1		ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5 linkuse as main transcript	c.1274C>A	p.Ala425Asp	missense_variant	11/12	1		ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.000949

AC:

105

AN:

110692

Hom.:

Cov.:

AF XY:

0.000608

AC XY:

AN XY:

32904

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000385

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:

0.000235

AC:

AN:

178975

Hom.:

AF XY:

0.0000781

AC XY:

AN XY:

63987

show subpopulations

Gnomad AFR exome

AF:

0.00320

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

126

AN:

1091206

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

357140

show subpopulations

Gnomad4 AFR exome

AF:

0.00418

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000561

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000196

GnomAD4 genome

AF:

0.000948

AC:

105

AN:

110732

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

AN XY:

32954

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.000384

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:

0.000123

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000206

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.2501C>A (p.A834D) alteration is located in exon 10 (coding exon 10) of the AMOT gene. This alteration results from a C to A substitution at nucleotide position 2501, causing the alanine (A) at amino acid position 834 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.025

T;.;T;T

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.65

T;T;T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;.;.;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.29

N;N;N;N

REVEL

Benign

0.019

Sift

Benign

0.13

T;.;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.090

B;.;.;B

Vest4

0.19

MVP

0.22

MPC

0.46

ClinPred

0.019

GERP RS

2.5

Varity_R

0.16

gMVP

0.12

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