Variant 11-94799830-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130847.3(AMOTL1):c.640G>A(p.Val214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AMOTL1
NM_130847.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360

Variant links:

Genes affected

AMOTL1 (HGNC:17811): (angiomotin like 1) The protein encoded by this gene is a peripheral membrane protein that is a component of tight junctions or TJs. TJs form an apical junctional structure and act to control paracellular permeability and maintain cell polarity. This protein is related to angiomotin, an angiostatin binding protein that regulates endothelial cell migration and capillary formation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

AMOTL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12123039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOTL1	NM_130847.3 linkuse as main transcript	c.640G>A	p.Val214Met	missense_variant	3/13	ENST00000433060.3	NP_570899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOTL1	ENST00000433060.3 linkuse as main transcript	c.640G>A	p.Val214Met	missense_variant	3/13	1	NM_130847.3	ENSP00000387739	P1	Q8IY63-1
AMOTL1	ENST00000317829.12 linkuse as main transcript	c.490G>A	p.Val164Met	missense_variant	2/12	1		ENSP00000320968		Q8IY63-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441044

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 29, 2021

The c.640G>A (p.V214M) alteration is located in exon 3 (coding exon 3) of the AMOTL1 gene. This alteration results from a G to A substitution at nucleotide position 640, causing the valine (V) at amino acid position 214 to be replaced by a methionine (M). 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

0.085

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.063

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.93

P;B

Vest4

0.26

MutPred

0.21

.;Loss of sheet (P = 0.0084);

MVP

0.34

MPC

0.26

ClinPred

0.50

GERP RS

3.0

Varity_R

0.049

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over