Genetic Variant AMER1:p.Arg1091Arg (chrX-64190014-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_152424.4(AMER1):c.3273G>A(p.Arg1091Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,204,719 control chromosomes in the GnomAD database, including 3 homozygotes. There are 235 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., 17 hem., cov: 22)

Exomes 𝑓: 0.00067 ( 3 hom. 218 hem. )

Consequence

AMER1
NM_152424.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.220

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: Genomics England PanelApp, G2P, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae)

AMER1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_152424.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-64190014-C-T is Benign according to our data. Variant chrX-64190014-C-T is described in ClinVar as Benign. ClinVar VariationId is 756273.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 17 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMER1	NM_152424.4	MANE Select	c.3273G>A	p.Arg1091Arg	synonymous	Exon 2 of 2	NP_689637.3	Q5JTC6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMER1	ENST00000374869.8	TSL:5 MANE Select	c.3273G>A	p.Arg1091Arg	synonymous	Exon 2 of 2	ENSP00000364003.4	Q5JTC6-1

Frequencies

GnomAD3 genomes

AF:

0.000442

AC:

AN:

110889

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00300

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000473

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000750

AC:

127

AN:

169375

AF XY:

0.000608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000340

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00331

Gnomad NFE exome

AF:

0.000652

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.000669

AC:

732

AN:

1093776

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

218

AN XY:

359588

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26368

American (AMR)

AF:

0.000287

AC:

AN:

34829

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19247

East Asian (EAS)

AF:

0.00

AC:

AN:

30100

South Asian (SAS)

AF:

0.000450

AC:

AN:

53317

European-Finnish (FIN)

AF:

0.00318

AC:

128

AN:

40218

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.000619

AC:

520

AN:

839700

Other (OTH)

AF:

0.00105

AC:

AN:

45882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000442

AC:

AN:

110943

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

33243

show subpopulations

African (AFR)

AF:

0.0000655

AC:

AN:

30513

American (AMR)

AF:

0.000380

AC:

AN:

10533

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3431

South Asian (SAS)

AF:

0.00

AC:

AN:

2618

European-Finnish (FIN)

AF:

0.00300

AC:

AN:

5999

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.000473

AC:

AN:

52809

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000327

Hom.:

Bravo

AF:

0.000264

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

0.22

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over