Genetic Variant NM_001113490.2:c.3160G>C (chrX-112778662-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001113490.2(AMOT):c.3160G>C(p.Gly1054Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000059 in 1,186,072 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000056 ( 0 hom. 2 hem. )

Consequence

AMOT
NM_001113490.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3177727).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.3160G>C	p.Gly1054Arg	missense splice_region	Exon 14 of 14	NP_001106962.1	Q4VCS5-1
AMOT	NM_001386998.1		c.3160G>C	p.Gly1054Arg	missense splice_region	Exon 15 of 15	NP_001373927.1	Q4VCS5-1
AMOT	NM_001386999.1		c.3160G>C	p.Gly1054Arg	missense splice_region	Exon 14 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.3160G>C	p.Gly1054Arg	missense splice_region	Exon 14 of 14	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5	TSL:1	c.2464G>C	p.Gly822Arg	missense splice_region	Exon 11 of 11	ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5	TSL:1	c.1933G>C	p.Gly645Arg	missense splice_region	Exon 12 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111602

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

176375

AF XY:

0.0000162

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000252

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000558

AC:

AN:

1074470

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

342118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25999

American (AMR)

AF:

0.00

AC:

AN:

34212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18928

East Asian (EAS)

AF:

0.00

AC:

AN:

29888

South Asian (SAS)

AF:

0.00

AC:

AN:

49970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39935

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4009

European-Non Finnish (NFE)

AF:

0.00000726

AC:

AN:

826399

Other (OTH)

AF:

0.00

AC:

AN:

45130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33792

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30629

American (AMR)

AF:

0.00

AC:

AN:

10559

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53135

Other (OTH)

AF:

0.00

AC:

AN:

1479

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

4.1

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.75

REVEL

Benign

0.094

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Polyphen

0.88

Vest4

0.47

MutPred

0.29

Gain of ubiquitination at K1051 (P = 0.0564)

MVP

0.49

MPC

1.1

ClinPred

0.52

GERP RS

6.0

Varity_R

0.36

gMVP

0.34

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over