Variant 4-70603887-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016519.6(AMBN):c.764C>T(p.Ala255Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 1,613,484 control chromosomes in the GnomAD database, including 4,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.094 ( 785 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4054 hom. )

Consequence

AMBN
NM_016519.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.878

Variant links:

Genes affected

AMBN (HGNC:452): (ameloblastin) This gene encodes the nonamelogenin enamel matrix protein ameloblastin. The encoded protein may be important in enamel matrix formation and mineralization. This gene is located in the calcium-binding phosphoprotein gene cluster on chromosome 4. Mutations in this gene may be associated with dentinogenesis imperfect and autosomal dominant amylogenesis imperfect. [provided by RefSeq, Aug 2011]

AMBN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027917027).

BP6

Variant 4-70603887-C-T is Benign according to our data. Variant chr4-70603887-C-T is described in ClinVar as [Benign]. Clinvar id is 3056421.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMBN	NM_016519.6 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	12/13	ENST00000322937.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMBN	ENST00000322937.10 linkuse as main transcript	c.764C>T	p.Ala255Val	missense_variant	12/13	1	NM_016519.6	P1	Q9NP70-1
AMBN	ENST00000449493.2 linkuse as main transcript	c.719C>T	p.Ala240Val	missense_variant	12/13	5			Q9NP70-2

Frequencies

GnomAD3 genomes

AF:

0.0944

AC:

14358

AN:

152028

Hom.:

786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0874

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0710

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0855

AC:

21442

AN:

250910

Hom.:

1024

AF XY:

0.0852

AC XY:

11556

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0676

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0884

GnomAD4 exome

AF:

0.0703

AC:

102713

AN:

1461338

Hom.:

4054

Cov.:

AF XY:

0.0717

AC XY:

52109

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0758

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0598

Gnomad4 OTH exome

AF:

0.0842

GnomAD4 genome

AF:

0.0944

AC:

14369

AN:

152146

Hom.:

785

Cov.:

AF XY:

0.0952

AC XY:

7085

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.0871

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0710

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.0758

Hom.:

1036

Bravo

AF:

0.0968

TwinsUK

AF:

0.0537

AC:

199

ALSPAC

AF:

0.0586

AC:

226

ESP6500AA

AF:

0.133

AC:

587

ESP6500EA

AF:

0.0721

AC:

620

ExAC

AF:

0.0868

AC:

10543

Asia WGS

AF:

0.136

AC:

474

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0669

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AMBN-related disorder

Benign:1

Benign, criteria provided, single submitter

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

0.18

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.81

P;P

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

D;.;D

REVEL

Benign

0.10

Sift

Uncertain

0.0020

D;.;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.89

P;.;.

Vest4

0.25

MPC

0.32

ClinPred

0.045

GERP RS

-0.77

Varity_R

0.26

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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