chrX-112779197-G-C

Variant names:

• chrX-112779197-G-C
• rs148609725
• NM_001113490.2:c.2957C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113490.2(AMOT):​c.2957C>G​(p.Pro986Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 111,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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

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=0.08943465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.2957C>G	p.Pro986Arg	missense_variant	Exon 13 of 14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.2957C>G	p.Pro986Arg	missense_variant	Exon 13 of 14	1	NM_001113490.2	ENSP00000361027.3
AMOT	ENST00000371962.5	c.2261C>G	p.Pro754Arg	missense_variant	Exon 10 of 11	1		ENSP00000361030.1
AMOT	ENST00000304758.5	c.1730C>G	p.Pro577Arg	missense_variant	Exon 11 of 12	1		ENSP00000305557.1

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111875 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 34037

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 12

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111929 Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1 AN XY: 34101

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.030	T;.;T;T
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.49	T;T;T;.
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.089	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.13	N;N;N;N
REVEL	Benign	0.010
Sift	Pathogenic	0.0	D;.;D;D
Sift4G	Uncertain	0.045	D;D;D;D
Polyphen		0.065	B;.;.;B
Vest4		0.30
MutPred		0.28		Loss of loop (P = 0.0128);.;.;Loss of loop (P = 0.0128);
MVP		0.34
MPC		0.33
ClinPred		0.25	T
GERP RS		2.0
Varity_R		0.079
gMVP		0.20

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

Other links and lift over

dbSNP: rs148609725; hg19: chrX-112022425;