3-134360150-C-T

Variant names:

• chr3-134360150-C-T
• rs777633596
• NM_016201.4:c.1839G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016201.4(AMOTL2):​c.1839G>A​(p.Glu613Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMOTL2 NM_016201.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 0 publications found

Genes affected

AMOTL2 (HGNC:17812): (angiomotin like 2) Angiomotin is a protein that binds angiostatin, a circulating inhibitor of the formation of new blood vessels (angiogenesis). Angiomotin mediates angiostatin inhibition of endothelial cell migration and tube formation in vitro. The protein encoded by this gene is related to angiomotin and is a member of the motin protein family. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016201.4. 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
	AMOTL2	NM_016201.4	MANE Select	c.1839G>A	p.Glu613Glu	synonymous	Exon 7 of 10	NP_057285.3
	AMOTL2	NM_001278683.1		c.2013G>A	p.Glu671Glu	synonymous	Exon 7 of 10	NP_001265612.1	Q9Y2J4-4
	AMOTL2	NM_001363943.2		c.1839G>A	p.Glu613Glu	synonymous	Exon 7 of 10	NP_001350872.1	Q9Y2J4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOTL2	ENST00000249883.10	TSL:1 MANE Select	c.1839G>A	p.Glu613Glu	synonymous	Exon 7 of 10	ENSP00000249883.5	Q9Y2J4-2
	AMOTL2	ENST00000513145.1	TSL:1	c.1833G>A	p.Glu611Glu	synonymous	Exon 7 of 10	ENSP00000425475.1	Q9Y2J4-3
	AMOTL2	ENST00000514516.5	TSL:2	c.2013G>A	p.Glu671Glu	synonymous	Exon 7 of 10	ENSP00000424765.1	Q9Y2J4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		-0.0080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.52		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777633596; hg19: chr3-134078992;