Variant X-64191566-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.1721G>A(p.Arg574Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,210,871 control chromosomes in the GnomAD database, including 1 homozygotes. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000024 ( 1 hom. 7 hem. )

Consequence

AMER1
NM_152424.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.591

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033424318).

BP6

Variant X-64191566-C-T is Benign according to our data. Variant chrX-64191566-C-T is described in ClinVar as [Benign]. Clinvar id is 133494.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER1	NM_152424.4 linkuse as main transcript	c.1721G>A	p.Arg574Gln	missense_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.1721G>A	p.Arg574Gln	missense_variant	2/2	5	NM_152424.4	ENSP00000364003.4		Q5JTC6-1

Frequencies

GnomAD3 genomes

AF:

0.0000622

AC:

AN:

112591

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34731

show subpopulations

Gnomad AFR

AF:

0.000161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

183160

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67622

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1098228

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363582

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000621

AC:

AN:

112643

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34793

show subpopulations

Gnomad4 AFR

AF:

0.000161

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1Other: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 14, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.019

Sift

Benign

0.21

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.041

B;B

Vest4

0.038

MVP

0.30

MPC

0.027

ClinPred

0.013

GERP RS

3.5

Varity_R

0.080

gMVP

0.033

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