rs34677493

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152424.4(AMER1):c.477T>G(p.Phe159Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 1,209,530 control chromosomes in the GnomAD database, including 4,387 homozygotes. There are 10,227 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 2151 hom., 3890 hem., cov: 23)

Exomes 𝑓: 0.019 ( 2236 hom. 6337 hem. )

Consequence

AMER1
NM_152424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -1.01

Variant links:

Genes affected

AMER1 (HGNC:26837): (APC membrane recruitment protein 1) The protein encoded by this gene upregulates trancriptional activation by the Wilms tumor protein and interacts with many other proteins, including CTNNB1, APC, AXIN1, and AXIN2. Defects in this gene are a cause of osteopathia striata with cranial sclerosis (OSCS). [provided by RefSeq, May 2010]

AMER1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.373587E-5).

BP6

Variant X-64192810-A-C is Benign according to our data. Variant chrX-64192810-A-C is described in ClinVar as [Benign]. Clinvar id is 133504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-64192810-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMER1	NM_152424.4 link	c.477T>G	p.Phe159Leu	missense_variant	Exon 2 of 2	ENST00000374869.8	NP_689637.3	Q5JTC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMER1	ENST00000374869.8 link	c.477T>G	p.Phe159Leu	missense_variant	Exon 2 of 2	5	NM_152424.4	ENSP00000364003.4		Q5JTC6-1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

14221

AN:

111475

Hom.:

2147

Cov.:

AF XY:

0.115

AC XY:

3868

AN XY:

33723

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0481

Gnomad ASJ

AF:

0.00530

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0263

Gnomad FIN

AF:

0.00246

Gnomad MID

AF:

0.0340

Gnomad NFE

AF:

0.00578

Gnomad OTH

AF:

0.0997

GnomAD3 exomes

AF:

0.0422

AC:

7715

AN:

182919

Hom.:

1074

AF XY:

0.0307

AC XY:

2070

AN XY:

67423

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.00643

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.00170

Gnomad NFE exome

AF:

0.00591

Gnomad OTH exome

AF:

0.0204

GnomAD4 exome

AF:

0.0193

AC:

21165

AN:

1098005

Hom.:

2236

Cov.:

AF XY:

0.0174

AC XY:

6337

AN XY:

363419

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.0255

Gnomad4 ASJ exome

AF:

0.00650

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.0339

Gnomad4 FIN exome

AF:

0.00198

Gnomad4 NFE exome

AF:

0.00510

Gnomad4 OTH exome

AF:

0.0386

GnomAD4 genome

AF:

0.128

AC:

14255

AN:

111525

Hom.:

2151

Cov.:

AF XY:

0.115

AC XY:

3890

AN XY:

33783

show subpopulations

Gnomad4 AFR

AF:

0.433

Gnomad4 AMR

AF:

0.0482

Gnomad4 ASJ

AF:

0.00530

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0264

Gnomad4 FIN

AF:

0.00246

Gnomad4 NFE

AF:

0.00578

Gnomad4 OTH

AF:

0.0991

Alfa

AF:

0.0269

Hom.:

1497

Bravo

AF:

0.147

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00450

AC:

ESP6500AA

AF:

0.439

AC:

1683

ESP6500EA

AF:

0.00624

AC:

ExAC

AF:

0.0469

AC:

5695

EpiCase

AF:

0.00627

EpiControl

AF:

0.00759

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-1.0

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.25

DANN

Benign

0.50

DEOGEN2

Benign

0.12

T;T

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.17

.;T

MetaRNN

Benign

0.000084

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.74

N;N

REVEL

Benign

0.024

Sift

Benign

0.30

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

B;B

Vest4

0.0090

MutPred

0.12

Loss of methylation at K158 (P = 0.0281);Loss of methylation at K158 (P = 0.0281);

MPC

0.026

ClinPred

0.0089

GERP RS

0.95

Varity_R

0.030

gMVP

0.071

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