X-112780981-T-G

Variant names:

• chrX-112780981-T-G
• rs145715476
• NM_001113490.2:c.2378A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001113490.2(AMOT):​c.2378A>C​(p.Asn793Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N793S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• 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]

MIR4329 (HGNC:38290): (microRNA 4329) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2378A>C	p.Asn793Thr	missense	Exon 12 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.2378A>C	p.Asn793Thr	missense	Exon 13 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.2378A>C	p.Asn793Thr	missense	Exon 12 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.2378A>C	p.Asn793Thr	missense	Exon 12 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.1682A>C	p.Asn561Thr	missense	Exon 9 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1151A>C	p.Asn384Thr	missense	Exon 10 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 112062 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 112062 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34232

African (AFR) AF: 0.00 AC: 0 AN: 30829

American (AMR) AF: 0.00 AC: 0 AN: 10604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2685

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53196

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.15
Sift	Benign	0.47	T
Sift4G	Benign	0.89	T
Polyphen		0.99	D
Vest4		0.64
MutPred		0.17		Gain of glycosylation at N793 (P = 0.0218)
MVP		0.72
MPC		0.31
ClinPred		0.73	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.17
Mutation Taster		=79/21	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: rs145715476; hg19: chrX-112024209;