dbSNP rs587778022: AMER1:p.Glu385_Glu387del (chrX-64192124-ACCTCTTCTT-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_152424.4(AMER1):c.1154_1162delAAGAAGAGG(p.Glu385_Glu387del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,204,948 control chromosomes in the GnomAD database, including 1 homozygotes. There are 178 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. E385E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.00041 ( 1 hom. 158 hem. )

Consequence

AMER1
NM_152424.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 3.34

Publications

0 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 -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_152424.4

BP6

Variant X-64192124-ACCTCTTCTT-A is Benign according to our data. Variant chrX-64192124-ACCTCTTCTT-A is described in ClinVar as Benign. ClinVar VariationId is 133486.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMER1	NM_152424.4 link	c.1154_1162delAAGAAGAGG	p.Glu385_Glu387del	disruptive_inframe_deletion	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.1154_1162delAAGAAGAGG	p.Glu385_Glu387del	disruptive_inframe_deletion	Exon 2 of 2	5	NM_152424.4	ENSP00000364003.4

Frequencies

GnomAD3 genomes

AF:

0.000489

AC:

AN:

108351

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000978

Gnomad ASJ

AF:

0.0172

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000116

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000852

AC:

156

AN:

183206

AF XY:

0.000901

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000410

AC:

450

AN:

1096597

Hom.:

AF XY:

0.000436

AC XY:

158

AN XY:

362007

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26372

American (AMR)

AF:

0.0000284

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.0174

AC:

338

AN:

19370

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40483

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.0000797

AC:

AN:

840694

Other (OTH)

AF:

0.000934

AC:

AN:

46044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

107

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:

0.000489

AC:

AN:

108351

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

AN XY:

31499

show subpopulations

African (AFR)

AF:

0.0000338

AC:

AN:

29611

American (AMR)

AF:

0.0000978

AC:

AN:

10230

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

AN:

2609

East Asian (EAS)

AF:

0.00

AC:

AN:

3416

South Asian (SAS)

AF:

0.00

AC:

AN:

2448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

227

European-Non Finnish (NFE)

AF:

0.000116

AC:

AN:

51937

Other (OTH)

AF:

0.00

AC:

AN:

1472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.000536

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 23, 2024

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

PhyloP100

3.3

Mutation Taster

=197/3

polymorphism (auto)

(source)

Splicing

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