Variant X-64190016-G-A 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.3271C>T(p.Arg1091Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,205,109 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 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 0.000090 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000034 ( 0 hom. 18 hem. )

Consequence

AMER1
NM_152424.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0190

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=0.020765781).

BP6

Variant X-64190016-G-A is Benign according to our data. Variant chrX-64190016-G-A is described in ClinVar as [Benign]. Clinvar id is 133493.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER1	NM_152424.4 linkuse as main transcript	c.3271C>T	p.Arg1091Trp	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.3271C>T	p.Arg1091Trp	missense_variant	2/2	5	NM_152424.4	ENSP00000364003.4		Q5JTC6-1

Frequencies

GnomAD3 genomes

AF:

0.0000899

AC:

AN:

111175

Hom.:

Cov.:

AF XY:

0.0000599

AC XY:

AN XY:

33399

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000760

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.0000649

AC:

AN:

169435

Hom.:

AF XY:

0.0000695

AC XY:

AN XY:

57535

show subpopulations

Gnomad AFR exome

AF:

0.000349

Gnomad AMR exome

AF:

0.0000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1093884

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

359690

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000665

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.0000249

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000899

AC:

AN:

111225

Hom.:

Cov.:

AF XY:

0.0000598

AC XY:

AN XY:

33461

show subpopulations

Gnomad4 AFR

AF:

0.000131

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000762

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.000658

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000296

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000497

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

Dec 18, 2023

- -

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

0.085

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.35

.;N

REVEL

Benign

0.093

Sift

Benign

0.18

.;T

Sift4G

Uncertain

0.0020

.;D

Polyphen

0.0080

B;B

Vest4

0.10

MVP

0.23

MPC

0.025

ClinPred

0.048

GERP RS

4.1

Varity_R

0.093

gMVP

0.13

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