Variant 13-25170488-G-T 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.1132C>A(p.Leu378Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,614,196 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 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

AMER2
NM_152704.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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=0.16823244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER2	NM_152704.4 linkuse as main transcript	c.1132C>A	p.Leu378Ile	missense_variant	1/1	ENST00000515384.2	NP_689917.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMER2	ENST00000515384.2 linkuse as main transcript	c.1132C>A	p.Leu378Ile	missense_variant	1/1		NM_152704.4	ENSP00000426528	P1	Q8N7J2-1
LINC01053	ENST00000656176.1 linkuse as main transcript	n.63+1457G>T		intron_variant, non_coding_transcript_variant
AMER2	ENST00000357816.2 linkuse as main transcript	c.782-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000350469		Q8N7J2-2

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

250326

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0000644

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:

0.0000462

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000282

AC:

412

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

190

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000197

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

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

Dec 21, 2022

The c.1132C>A (p.L378I) 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 1132, causing the leucine (L) at amino acid position 378 to be replaced by an isoleucine (I). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

Eigen

Benign

0.095

Eigen_PC

Benign

0.042

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

M_CAP

Benign

0.0091

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.4

REVEL

Benign

0.17

Sift

Uncertain

0.013

Sift4G

Uncertain

0.026

Polyphen

0.99

Vest4

0.38

MVP

0.11

ClinPred

0.24

GERP RS

2.3

Varity_R

0.17

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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