Variant X-112778650-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000371959.9(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. 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
ENST00000371959.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.92

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38880682).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2 linkuse as main transcript	c.3172C>T	p.His1058Tyr	missense_variant	14/14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9 linkuse as main transcript	c.3172C>T	p.His1058Tyr	missense_variant	14/14	1	NM_001113490.2	ENSP00000361027	P3	Q4VCS5-1
AMOT	ENST00000371962.5 linkuse as main transcript	c.2476C>T	p.His826Tyr	missense_variant	11/11	1		ENSP00000361030	A2
AMOT	ENST00000304758.5 linkuse as main transcript	c.1945C>T	p.His649Tyr	missense_variant	12/12	1		ENSP00000305557	A2	Q4VCS5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000554

AC:

AN:

180567

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65355

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 SAS exome

AF:

0.0000544

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000968

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.3172C>T (p.H1058Y) alteration is located in exon 11 (coding exon 11) of the AMOT gene. This alteration results from a C to T substitution at nucleotide position 3172, causing the histidine (H) at amino acid position 1058 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

T;.;T;T

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.77

T;T;T;.

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.;.;L

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.57

N;N;N;N

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Benign

0.65

T;T;T;T

Polyphen

0.92

P;.;.;P

Vest4

0.48

MutPred

0.32

Gain of sheet (P = 0.0221);.;.;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

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