NM_001113490.2:c.2384G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001113490.2(AMOT):​c.2384G>T​(p.Gly795Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

AMOT
NM_001113490.2 missense

Scores

2
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMOTNM_001113490.2 linkc.2384G>T p.Gly795Val missense_variant Exon 12 of 14 ENST00000371959.9 NP_001106962.1 Q4VCS5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMOTENST00000371959.9 linkc.2384G>T p.Gly795Val missense_variant Exon 12 of 14 1 NM_001113490.2 ENSP00000361027.3 Q4VCS5-1
AMOTENST00000371962.5 linkc.1688G>T p.Gly563Val missense_variant Exon 9 of 11 1 ENSP00000361030.1 E7ERM3
AMOTENST00000304758.5 linkc.1157G>T p.Gly386Val missense_variant Exon 10 of 12 1 ENSP00000305557.1 Q4VCS5-2
AMOTENST00000371958.1 linkc.1688G>T p.Gly563Val missense_variant Exon 9 of 9 5 ENSP00000361026.1 A6NP16

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2384G>T (p.G795V) alteration is located in exon 9 (coding exon 9) of the AMOT gene. This alteration results from a G to T substitution at nucleotide position 2384, causing the glycine (G) at amino acid position 795 to be replaced by a valine (V). 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
0.16
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.;T;T;T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;T;T;.;T
M_CAP
Pathogenic
0.60
D
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.0
M;.;.;M;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-2.3
N;N;N;N;D
REVEL
Benign
0.12
Sift
Uncertain
0.020
D;.;D;D;D
Sift4G
Benign
0.084
T;T;T;T;T
Polyphen
0.95
P;.;.;P;.
Vest4
0.67
MutPred
0.20
Loss of catalytic residue at A794 (P = 0.0625);.;.;Loss of catalytic residue at A794 (P = 0.0625);.;
MVP
0.42
MPC
0.38
ClinPred
0.91
D
GERP RS
5.7
Varity_R
0.58
gMVP
0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-112024203; API