chrX-112780981-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001113490.2(AMOT):c.2378A>G(p.Asn793Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,210,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 40 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Publications

1 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:

MIR4329 (HGNC:38290): (microRNA 4329) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4329 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1309804).

BS2

High Hemizygotes in GnomAdExome4 at 40 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.2378A>G	p.Asn793Ser	missense	Exon 12 of 14	NP_001106962.1	Q4VCS5-1
AMOT	NM_001386998.1		c.2378A>G	p.Asn793Ser	missense	Exon 13 of 15	NP_001373927.1	Q4VCS5-1
AMOT	NM_001386999.1		c.2378A>G	p.Asn793Ser	missense	Exon 12 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.2378A>G	p.Asn793Ser	missense	Exon 12 of 14	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5	TSL:1	c.1682A>G	p.Asn561Ser	missense	Exon 9 of 11	ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5	TSL:1	c.1151A>G	p.Asn384Ser	missense	Exon 10 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

112062

Hom.:

Cov.:

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:

0.000113

Gnomad OTH

AF:

0.000663

GnomAD2 exomes

AF:

0.0000491

AC:

AN:

183418

AF XY:

0.0000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000117

AC:

129

AN:

1098216

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

363572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.0000284

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000147

AC:

124

AN:

842121

Other (OTH)

AF:

0.0000868

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.0000624

AC:

AN:

112114

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30896

American (AMR)

AF:

0.00

AC:

AN:

10617

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00

AC:

AN:

2677

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53189

Other (OTH)

AF:

0.000655

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

4.8

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.50

REVEL

Benign

0.10

Sift

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.89

Vest4

0.45

MVP

0.77

MPC

0.25

ClinPred

0.19

GERP RS

5.7

Varity_R

0.23

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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