Variant 4-70599585-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016519.6(AMBN):c.233G>T(p.Gly78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,613,588 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

AMBN
NM_016519.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.38

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023509592).

BP6

Variant 4-70599585-G-T is Benign according to our data. Variant chr4-70599585-G-T is described in ClinVar as [Benign]. Clinvar id is 3053002.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBN	NM_016519.6 link	c.233G>T	p.Gly78Val	missense_variant	5/13	ENST00000322937.10	NP_057603.1	Q9NP70-1Q546D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10 link	c.233G>T	p.Gly78Val	missense_variant	5/13	1	NM_016519.6	ENSP00000313809.6		Q9NP70-1
AMBN	ENST00000449493.2 link	c.233G>T	p.Gly78Val	missense_variant	5/13	5		ENSP00000391234.2		Q9NP70-2

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000861

AC:

216

AN:

250954

Hom.:

AF XY:

0.000686

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000344

AC:

503

AN:

1461470

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

200

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00374

AC:

569

AN:

152118

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.00387

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.00450

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00109

AC:

132

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMBN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.6

L;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.8

D;.;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;.;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.81

MVP

0.81

MPC

0.41

ClinPred

0.074

GERP RS

4.0

Varity_R

0.54

gMVP

0.41

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