NM_001113490.2:c.2479C>T

Variant names:

• chrX-112779675-G-A
• rs759471559
• NM_001113490.2:c.2479C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001113490.2(AMOT):​c.2479C>T​(p.Leu827Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000363 in 1,184,660 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.000027 (0 hom. 11 hem.)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOT	NM_001113490.2	MANE Select	c.2479C>T	p.Leu827Phe	missense	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.2479C>T	p.Leu827Phe	missense	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.2479C>T	p.Leu827Phe	missense	Exon 13 of 14	NP_001373928.1	Q4VCS5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOT	ENST00000371959.9	TSL:1 MANE Select	c.2479C>T	p.Leu827Phe	missense	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.1783C>T	p.Leu595Phe	missense	Exon 10 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1252C>T	p.Leu418Phe	missense	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 14 AN: 110707 Hom.: 0 Cov.: 22

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: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000412 AC: 7 AN: 169720 AF XY: 0.0000533

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: 0.0000791

Gnomad OTH exome AF: 0.000241

GnomAD4 exome AF: 0.0000270 AC: 29 AN: 1073953 Hom.: 0 Cov.: 30 AF XY: 0.0000320 AC XY: 11 AN XY: 343921

African (AFR) AF: 0.00 AC: 0 AN: 25962

American (AMR) AF: 0.00 AC: 0 AN: 33910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18494

East Asian (EAS) AF: 0.00 AC: 0 AN: 29742

South Asian (SAS) AF: 0.00 AC: 0 AN: 51312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39987

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4006

European-Non Finnish (NFE) AF: 0.0000339 AC: 28 AN: 825521

Other (OTH) AF: 0.0000222 AC: 1 AN: 45019

GnomAD4 genome AF: 0.000126 AC: 14 AN: 110707 Hom.: 0 Cov.: 22 AF XY: 0.0000912 AC XY: 3 AN XY: 32905

African (AFR) AF: 0.00 AC: 0 AN: 30369

American (AMR) AF: 0.00 AC: 0 AN: 10367

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2563

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000265 AC: 14 AN: 52916

Other (OTH) AF: 0.00 AC: 0 AN: 1485

Alfa AF: 0.000486 Hom.: 2

Bravo AF: 0.0000491

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.38		Loss of disorder (P = 0.0906)
MVP		0.75
MPC		0.33
ClinPred		0.31	T
GERP RS		5.3
Varity_R		0.72
gMVP		0.34
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs759471559; hg19: chrX-112022903;