Variant chr13-25170232-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152704.4(AMER2):c.1388C>A(p.Ala463Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,612,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

AMER2
NM_152704.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

AMER2 (HGNC:26360): (APC membrane recruitment protein 2) Enables phosphatidylinositol-4,5-bisphosphate binding activity. Involved in negative regulation of canonical Wnt signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AMER2 links:

LINC01053 (HGNC:):

LINC01053 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02679792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER2	NM_152704.4 linkuse as main transcript	c.1388C>A	p.Ala463Glu	missense_variant	1/1	ENST00000515384.2	NP_689917.2	Q8N7J2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMER2	ENST00000515384.2 linkuse as main transcript	c.1388C>A	p.Ala463Glu	missense_variant	1/1	6	NM_152704.4	ENSP00000426528.1	Q8N7J2-1
AMER2	ENST00000357816.2 linkuse as main transcript	c.1031C>A	p.Ala344Glu	missense_variant	3/3	2		ENSP00000350469.2	Q8N7J2-2
LINC01053	ENST00000656176.1 linkuse as main transcript	n.63+1201G>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000252

AC:

AN:

245598

Hom.:

AF XY:

0.000293

AC XY:

AN XY:

133062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000158

AC:

230

AN:

1459932

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

137

AN XY:

726098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000729

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000158

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000272

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.1388C>A (p.A463E) alteration is located in exon 1 (coding exon 1) of the AMER2 gene. This alteration results from a C to A substitution at nucleotide position 1388, causing the alanine (A) at amino acid position 463 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

.;T

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.12

Sift

Benign

0.27

T;T

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.14

MVP

0.085

ClinPred

0.12

GERP RS

4.6

Varity_R

0.18

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over