rs34677493

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

osteopathia striata with cranial sclerosis
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Genomics England PanelApp, Orphanet, G2P

AMER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 133504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.:

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

GnomAD2 exomes

AF:

0.0422

AC:

7715

AN:

182919

AF XY:

0.0307

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 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

African (AFR)

AF:

0.453

AC:

11931

AN:

26358

American (AMR)

AF:

0.0255

AC:

898

AN:

35169

Ashkenazi Jewish (ASJ)

AF:

0.00650

AC:

126

AN:

19378

East Asian (EAS)

AF:

0.0000993

AC:

AN:

30204

South Asian (SAS)

AF:

0.0339

AC:

1834

AN:

54123

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

40499

Middle Eastern (MID)

AF:

0.0533

AC:

220

AN:

4129

European-Non Finnish (NFE)

AF:

0.00510

AC:

4296

AN:

842075

Other (OTH)

AF:

0.0386

AC:

1777

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

686

1372

2058

2744

3430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.128

AC:

14255

AN:

111525

Hom.:

2151

Cov.:

AF XY:

0.115

AC XY:

3890

AN XY:

33783

show subpopulations

African (AFR)

AF:

0.433

AC:

13179

AN:

30436

American (AMR)

AF:

0.0482

AC:

512

AN:

10626

Ashkenazi Jewish (ASJ)

AF:

0.00530

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3525

South Asian (SAS)

AF:

0.0264

AC:

AN:

2653

European-Finnish (FIN)

AF:

0.00246

AC:

AN:

6107

Middle Eastern (MID)

AF:

0.0376

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00578

AC:

307

AN:

53126

Other (OTH)

AF:

0.0991

AC:

150

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

320

639

959

1278

1598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0522

Hom.:

3500

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

- -

Jun 15, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

(source)

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

PhyloP100

-1.0

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over