Variant X-64190014-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 756273.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-64190014-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER1	NM_152424.4 linkuse as main transcript	c.3273G>A	p.Arg1091Arg	synonymous_variant	2/2	ENST00000374869.8	NP_689637.3	Q5JTC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMER1	ENST00000374869.8 linkuse as main transcript	c.3273G>A	p.Arg1091Arg	synonymous_variant	2/2	5	NM_152424.4	ENSP00000364003.4		Q5JTC6-1

Frequencies

GnomAD3 genomes

AF:

0.000442

AC:

AN:

110889

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

33181

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

GnomAD3 exomes

AF:

0.000750

AC:

127

AN:

169375

Hom.:

AF XY:

0.000608

AC XY:

AN XY:

57583

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 SAS exome

AF:

0.000343

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

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000450

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.000619

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000442

AC:

AN:

110943

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

33243

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.000380

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00300

Gnomad4 NFE

AF:

0.000473

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

DANN

Benign

0.41

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