Variant 4-70518820-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000339336.9(AMTN):c.43C>T(p.Arg15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,604,560 control chromosomes in the GnomAD database, including 14,534 homozygotes. 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 (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1081 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13453 hom. )

Consequence

AMTN
ENST00000339336.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.32

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011405349).

BP6

Variant 4-70518820-C-T is Benign according to our data. Variant chr4-70518820-C-T is described in ClinVar as [Benign]. Clinvar id is 3058967.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMTN	NM_212557.4 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	2/9	ENST00000339336.9	NP_997722.1
AMTN	NM_001286731.2 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	2/9		NP_001273660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMTN	ENST00000339336.9 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	2/9	1	NM_212557.4	ENSP00000341013	P4	Q6UX39-1
AMTN	ENST00000504451.1 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	2/9	1		ENSP00000422452	A2	Q6UX39-2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15834

AN:

152082

Hom.:

1075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0846

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.127

AC:

31960

AN:

250934

Hom.:

2262

AF XY:

0.132

AC XY:

17964

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0923

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.0898

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.131

AC:

190276

AN:

1452360

Hom.:

13453

Cov.:

AF XY:

0.133

AC XY:

95979

AN XY:

722912

show subpopulations

Gnomad4 AFR exome

AF:

0.0280

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.0962

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.104

AC:

15839

AN:

152200

Hom.:

1081

Cov.:

AF XY:

0.103

AC XY:

7698

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0846

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.134

Hom.:

2490

Bravo

AF:

0.104

TwinsUK

AF:

0.141

AC:

522

ALSPAC

AF:

0.128

AC:

495

ESP6500AA

AF:

0.0315

AC:

139

ESP6500EA

AF:

0.139

AC:

1198

ExAC

AF:

0.127

AC:

15422

Asia WGS

AF:

0.159

AC:

551

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMTN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as 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

0.12

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

0.077

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.063

Sift

Benign

0.057

T;T

Sift4G

Benign

0.068

T;D

Polyphen

0.92

P;P

Vest4

0.12

MPC

0.18

ClinPred

0.0094

GERP RS

4.9

Varity_R

0.13

gMVP

0.15

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