chrX-112779653-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A834G) has been classified as Uncertain significance.

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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 715211.

BS2

High Hemizygotes in GnomAd4 at 20 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113490.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOT	NM_001113490.2	MANE Select	c.2501C>A	p.Ala834Asp	missense	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
AMOT	NM_001386998.1		c.2501C>A	p.Ala834Asp	missense	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
AMOT	NM_001386999.1		c.2501C>A	p.Ala834Asp	missense	Exon 13 of 14	NP_001373928.1	Q4VCS5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOT	ENST00000371959.9	TSL:1 MANE Select	c.2501C>A	p.Ala834Asp	missense	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5	TSL:1	c.1805C>A	p.Ala602Asp	missense	Exon 10 of 11	ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5	TSL:1	c.1274C>A	p.Ala425Asp	missense	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.000949

AC:

105

AN:

110692

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000235

AC:

AN:

178975

AF XY:

0.0000781

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 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

African (AFR)

AF:

0.00418

AC:

110

AN:

26314

American (AMR)

AF:

0.000114

AC:

AN:

34995

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19155

East Asian (EAS)

AF:

0.00

AC:

AN:

30036

South Asian (SAS)

AF:

0.0000561

AC:

AN:

53488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4093

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

836976

Other (OTH)

AF:

0.000196

AC:

AN:

45803

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000948

AC:

105

AN:

110732

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

AN XY:

32954

show subpopulations

African (AFR)

AF:

0.00332

AC:

101

AN:

30422

American (AMR)

AF:

0.000384

AC:

AN:

10406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.00

AC:

AN:

2547

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52881

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000373

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000206

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.025

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.65

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

1.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.29

REVEL

Benign

0.019

Sift

Benign

0.13

Sift4G

Benign

0.22

Polyphen

0.090

Vest4

0.19

MVP

0.22

MPC

0.46

ClinPred

0.019

GERP RS

2.5

Varity_R

0.16

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over