Variant 4-70524930-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000339336.9(AMTN):c.263G>A(p.Gly88Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,613,988 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 8 hom. )

Consequence

AMTN
ENST00000339336.9 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.80

Variant links:

Genes affected

AMTN (HGNC:33188): (amelotin) The mineralized portions of teeth, the dentin and enamel, are formed by mesenchyme-derived odontoblasts and epithelium-derived ameloblasts, respectively. As ameloblasts differentiate, they deposit specific proteins necessary for enamel formation, including amelogenin (AMELX; MIM 300391), enamelin (ENAM; MIM 606585), and ameloblastin (AMBN; MIM 601259), in the organic enamel matrix. Amelotin is specifically expressed in maturation-stage ameloblasts (Iwasaki et al., 2005 [PubMed 16304441]).[supplied by OMIM, Mar 2008]

AMTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006739855).

BP6

Variant 4-70524930-G-A is Benign according to our data. Variant chr4-70524930-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046216.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMTN	NM_212557.4 linkuse as main transcript	c.263G>A	p.Gly88Glu	missense_variant	5/9	ENST00000339336.9	NP_997722.1
AMTN	NM_001286731.2 linkuse as main transcript	c.260G>A	p.Gly87Glu	missense_variant	5/9		NP_001273660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMTN	ENST00000339336.9 linkuse as main transcript	c.263G>A	p.Gly88Glu	missense_variant	5/9	1	NM_212557.4	ENSP00000341013	P4	Q6UX39-1
AMTN	ENST00000504451.1 linkuse as main transcript	c.260G>A	p.Gly87Glu	missense_variant	5/9	1		ENSP00000422452	A2	Q6UX39-2

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00213

AC:

535

AN:

251114

Hom.:

AF XY:

0.00222

AC XY:

301

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00291

AC:

4257

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

2022

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

152256

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00230

AC:

279

EpiCase

AF:

0.00365

EpiControl

AF:

0.00362

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMTN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 15, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.096

DANN

Benign

0.31

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.038

Sift

Benign

0.74

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.013

B;B

Vest4

0.32

MVP

0.088

MPC

0.13

ClinPred

0.0046

GERP RS

-7.3

Varity_R

0.039

gMVP

0.17

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