3-134360154-T-A

Variant names:

• chr3-134360154-T-A
• rs371941299
• NM_016201.4:c.1835A>T

Variant summary

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

The NM_016201.4(AMOTL2):​c.1835A>T​(p.Asn612Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N612S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AMOTL2 NM_016201.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40
• 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 2 ACMG points.

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

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.1835A>T	p.Asn612Ile	missense	Exon 7 of 10	NP_057285.3
	AMOTL2	NM_001278683.1		c.2009A>T	p.Asn670Ile	missense	Exon 7 of 10	NP_001265612.1	Q9Y2J4-4
	AMOTL2	NM_001363943.2		c.1835A>T	p.Asn612Ile	missense	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.1835A>T	p.Asn612Ile	missense	Exon 7 of 10	ENSP00000249883.5	Q9Y2J4-2
	AMOTL2	ENST00000513145.1	TSL:1	c.1829A>T	p.Asn610Ile	missense	Exon 7 of 10	ENSP00000425475.1	Q9Y2J4-3
	AMOTL2	ENST00000514516.5	TSL:2	c.2009A>T	p.Asn670Ile	missense	Exon 7 of 10	ENSP00000424765.1	Q9Y2J4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461500 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726948

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111776

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Benign	0.040	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.17		Gain of helix (P = 0.0696)
MVP		0.52
MPC		0.68
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.50
Mutation Taster		=82/18	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: rs371941299; hg19: chr3-134078996;