rs767240686

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_212557.4(AMTN):c.288C>A(p.His96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AMTN
NM_212557.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.241

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

amelogenesis imperfecta, type 3A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
amelogenesis imperfecta type 3B
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

AMTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018541217).

BP6

Variant 4-70524955-C-A is Benign according to our data. Variant chr4-70524955-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2555226.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212557.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMTN	NM_212557.4	MANE Select	c.288C>A	p.His96Gln	missense	Exon 5 of 9	NP_997722.1	F1T0L8
	AMTN	NM_001286731.2		c.285C>A	p.His95Gln	missense	Exon 5 of 9	NP_001273660.1	Q6UX39-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMTN	ENST00000339336.9	TSL:1 MANE Select	c.288C>A	p.His96Gln	missense	Exon 5 of 9	ENSP00000341013.4	Q6UX39-1
	AMTN	ENST00000504451.1	TSL:1	c.285C>A	p.His95Gln	missense	Exon 5 of 9	ENSP00000422452.1	Q6UX39-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251046

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111664

Other (OTH)

AF:

0.0000497

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.024

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.35

M_CAP

Benign

0.0016

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

PhyloP100

-0.24

PrimateAI

Benign

0.42

PROVEAN

Benign

3.4

REVEL

Benign

0.039

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.16

MutPred

0.23

Loss of glycosylation at P97 (P = 0.0882)

MVP

0.35

MPC

0.068

ClinPred

0.033

GERP RS

-2.6

Varity_R

0.029

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over