NM_130847.3:c.277G>A

Variant names:

• chr11-94799467-G-A
• NM_130847.3:c.277G>A

Variant summary

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

The NM_130847.3(AMOTL1):​c.277G>A​(p.Ala93Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AMOTL1 NM_130847.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00

Genes affected

AMOTL1 (HGNC:17811): (angiomotin like 1) The protein encoded by this gene is a peripheral membrane protein that is a component of tight junctions or TJs. TJs form an apical junctional structure and act to control paracellular permeability and maintain cell polarity. This protein is related to angiomotin, an angiostatin binding protein that regulates endothelial cell migration and capillary formation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

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=0.17239162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMOTL1	NM_130847.3	c.277G>A	p.Ala93Thr	missense_variant	Exon 3 of 13	ENST00000433060.3	NP_570899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMOTL1	ENST00000433060.3	c.277G>A	p.Ala93Thr	missense_variant	Exon 3 of 13	1	NM_130847.3	ENSP00000387739.2
AMOTL1	ENST00000317829.12	c.127G>A	p.Ala43Thr	missense_variant	Exon 2 of 12	1		ENSP00000320968.8
AMOTL1	ENST00000299004.13	c.364G>A	p.Ala122Thr	missense_variant	Exon 5 of 5	2		ENSP00000299004.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457542 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724566

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.;T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	.;.;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.058
Sift	Uncertain	0.026	D;T;T
Sift4G	Uncertain	0.032	D;T;T
Polyphen		0.0010	.;B;B
Vest4		0.21, 0.15
MutPred		0.17		.;.;Gain of phosphorylation at A93 (P = 0.0662);
MVP		0.41
MPC		0.25
ClinPred		0.67	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94532633;