Genetic Variant AMOT:p.His1058Tyr (chrX-112778650-G-A) – 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.3172C>T(p.His1058Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,085,889 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 3 hem. )

Consequence

AMOT
NM_001113490.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.92

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=0.38880682).

BS2

High Hemizygotes in GnomAdExome4 at 3 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.3172C>T	p.His1058Tyr	missense	Exon 14 of 14	NP_001106962.1	Q4VCS5-1
AMOT	NM_001386998.1		c.3172C>T	p.His1058Tyr	missense	Exon 15 of 15	NP_001373927.1	Q4VCS5-1
AMOT	NM_001386999.1		c.3172C>T	p.His1058Tyr	missense	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.3172C>T	p.His1058Tyr	missense	Exon 14 of 14	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5	TSL:1	c.2476C>T	p.His826Tyr	missense	Exon 11 of 11	ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5	TSL:1	c.1945C>T	p.His649Tyr	missense	Exon 12 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000554

AC:

AN:

180567

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000460

AC:

AN:

1085889

Hom.:

Cov.:

AF XY:

0.00000851

AC XY:

AN XY:

352365

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26227

American (AMR)

AF:

0.00

AC:

AN:

34891

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19148

East Asian (EAS)

AF:

0.00

AC:

AN:

30042

South Asian (SAS)

AF:

0.0000968

AC:

AN:

51668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4071

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834136

Other (OTH)

AF:

0.00

AC:

AN:

45558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

8.9

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.57

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.65

Polyphen

0.92

Vest4

0.48

MutPred

0.32

Gain of sheet (P = 0.0221)

MVP

0.47

MPC

1.1

ClinPred

0.57

GERP RS

6.0

Varity_R

0.45

gMVP

0.29

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over