rs587778024

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152424.4(AMER1):c.835A>G(p.Ser279Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 1,204,729 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000092 ( 0 hom. 4 hem. )

Consequence

AMER1
NM_152424.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.0690

Publications

1 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0635325).

BP6

Variant X-64192452-T-C is Benign according to our data. Variant chrX-64192452-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 133491.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMER1	NM_152424.4 link	c.835A>G	p.Ser279Gly	missense_variant	Exon 2 of 2	ENST00000374869.8	NP_689637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMER1	ENST00000374869.8 link	c.835A>G	p.Ser279Gly	missense_variant	Exon 2 of 2	5	NM_152424.4	ENSP00000364003.4

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113368

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:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000348

AC:

AN:

172544

AF XY:

0.0000513

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000257

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000916

AC:

AN:

1091361

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

357799

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26134

American (AMR)

AF:

0.00

AC:

AN:

34490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18806

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30176

South Asian (SAS)

AF:

0.00

AC:

AN:

52474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40115

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4080

European-Non Finnish (NFE)

AF:

0.00000953

AC:

AN:

839313

Other (OTH)

AF:

0.0000218

AC:

AN:

45773

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00000882

AC:

AN:

113368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31227

American (AMR)

AF:

0.00

AC:

AN:

10824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.000280

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2833

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53429

Other (OTH)

AF:

0.00

AC:

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000868

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Mar 04, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

0.073

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.17

T;T

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.50

.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;L

PhyloP100

0.069

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.015

Sift

Benign

0.30

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0020

B;B

Vest4

0.10

MutPred

0.32

Loss of phosphorylation at S279 (P = 0.0058);Loss of phosphorylation at S279 (P = 0.0058);

MVP

0.21

MPC

0.024

ClinPred

0.045

GERP RS

-0.012

Varity_R

0.030

gMVP

0.10

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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