Variant 13-25170137-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152704.4(AMER2):c.1483C>T(p.Arg495Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

AMER2
NM_152704.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426

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:49047): (long intergenic non-protein coding RNA 1053)

LINC01053 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19748479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMER2	NM_152704.4 linkuse as main transcript	c.1483C>T	p.Arg495Trp	missense_variant	1/1	ENST00000515384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMER2	ENST00000515384.2 linkuse as main transcript	c.1483C>T	p.Arg495Trp	missense_variant	1/1		NM_152704.4	P1	Q8N7J2-1
LINC01053	ENST00000656176.1 linkuse as main transcript	n.63+1106G>A		intron_variant, non_coding_transcript_variant
AMER2	ENST00000357816.2 linkuse as main transcript	c.1126C>T	p.Arg376Trp	missense_variant	3/3	2			Q8N7J2-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251112

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000193

Hom.:

ExAC

AF:

0.00000824

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

Jul 21, 2021

The c.1483C>T (p.R495W) alteration is located in exon 1 (coding exon 1) of the AMER2 gene. This alteration results from a C to T substitution at nucleotide position 1483, causing the arginine (R) at amino acid position 495 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.73

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.12

Sift

Benign

0.11

T;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.14

MutPred

0.43

.;Gain of catalytic residue at L493 (P = 0);

MVP

0.18

ClinPred

0.93

GERP RS

1.8

Varity_R

0.084

gMVP

0.12

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