NM_001113490.2:c.2488G>A

Variant names:

• chrX-112779666-C-T
• rs145727995
• NM_001113490.2:c.2488G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001113490.2(AMOT):​c.2488G>A​(p.Gly830Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,190,326 control chromosomes in the GnomAD database, including 1 homozygotes. There are 409 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00071 (0 hom., 24 hem., cov: 22)
  • Exomes 𝑓: 0.0011 (1 hom. 385 hem.)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013961524).
• BS2: High Hemizygotes in GnomAd4 at 24 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.2488G>A	p.Gly830Arg	missense	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.2488G>A	p.Gly830Arg	missense	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.2488G>A	p.Gly830Arg	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.2488G>A	p.Gly830Arg	missense	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.1792G>A	p.Gly598Arg	missense	Exon 10 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1261G>A	p.Gly421Arg	missense	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes AF: 0.000706 AC: 78 AN: 110540 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000392

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00135

GnomAD2 exomes AF: 0.000815 AC: 141 AN: 173074 AF XY: 0.00100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000919

Gnomad OTH exome AF: 0.000944

GnomAD4 exome AF: 0.00111 AC: 1197 AN: 1079748 Hom.: 1 Cov.: 30 AF XY: 0.00110 AC XY: 385 AN XY: 348424

African (AFR) AF: 0.000307 AC: 8 AN: 26071

American (AMR) AF: 0.00194 AC: 66 AN: 34097

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18688

East Asian (EAS) AF: 0.00 AC: 0 AN: 29793

South Asian (SAS) AF: 0.000691 AC: 36 AN: 52069

European-Finnish (FIN) AF: 0.0000499 AC: 2 AN: 40115

Middle Eastern (MID) AF: 0.000247 AC: 1 AN: 4041

European-Non Finnish (NFE) AF: 0.00124 AC: 1029 AN: 829616

Other (OTH) AF: 0.00122 AC: 55 AN: 45258

GnomAD4 genome AF: 0.000705 AC: 78 AN: 110578 Hom.: 0 Cov.: 22 AF XY: 0.000732 AC XY: 24 AN XY: 32802

African (AFR) AF: 0.000231 AC: 7 AN: 30368

American (AMR) AF: 0.00125 AC: 13 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.000394 AC: 1 AN: 2538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00104 AC: 55 AN: 52842

Other (OTH) AF: 0.00133 AC: 2 AN: 1500

Alfa AF: 0.00109 Hom.: 58

Bravo AF: 0.000820

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.000717 AC: 87

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	0.24
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.075
Sift	Benign	0.14	T
Sift4G	Benign	0.32	T
Polyphen		0.93	P
Vest4		0.096
MutPred		0.34		Gain of MoRF binding (P = 0.0184)
MVP		0.37
MPC		0.37
ClinPred		0.054	T
GERP RS		4.3
Varity_R		0.13
gMVP		0.057
Mutation Taster		=98/2	polymorphism (auto)

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: rs145727995; hg19: chrX-112022894;