NM_016201.4:c.1812G>C

Variant names:

• chr3-134360177-C-G
• rs151045996
• NM_016201.4:c.1812G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016201.4(AMOTL2):​c.1812G>C​(p.Gln604His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: AMOTL2 NM_016201.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0740
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.062159926).

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.1812G>C	p.Gln604His	missense	Exon 7 of 10	NP_057285.3
	AMOTL2	NM_001278683.1		c.1986G>C	p.Gln662His	missense	Exon 7 of 10	NP_001265612.1	Q9Y2J4-4
	AMOTL2	NM_001363943.2		c.1812G>C	p.Gln604His	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.1812G>C	p.Gln604His	missense	Exon 7 of 10	ENSP00000249883.5	Q9Y2J4-2
	AMOTL2	ENST00000513145.1	TSL:1	c.1806G>C	p.Gln602His	missense	Exon 7 of 10	ENSP00000425475.1	Q9Y2J4-3
	AMOTL2	ENST00000514516.5	TSL:2	c.1986G>C	p.Gln662His	missense	Exon 7 of 10	ENSP00000424765.1	Q9Y2J4-4

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000248 AC: 62 AN: 249588 AF XY: 0.000281

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000930

Gnomad NFE exome AF: 0.000490

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000462 AC: 676 AN: 1461720 Hom.: 0 Cov.: 32 AF XY: 0.000436 AC XY: 317 AN XY: 727148

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000576 AC: 641 AN: 1111922

Other (OTH) AF: 0.000282 AC: 17 AN: 60390

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000320 Hom.: 0

Bravo AF: 0.000261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000247 AC: 30

EpiCase AF: 0.000164

EpiControl AF: 0.000594

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	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.074
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.061
Sift	Benign	0.053	T
Sift4G	Benign	0.19	T
Polyphen		0.052	B
Vest4		0.17
MutPred		0.16		Gain of glycosylation at P603 (P = 0.0887)
MVP		0.32
MPC		0.57
ClinPred		0.047	T
GERP RS		4.1
Varity_R		0.15
gMVP		0.37
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151045996; hg19: chr3-134079019;