chr4-70524911-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_212557.4(AMTN):​c.244C>A​(p.His82Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

AMTN
NM_212557.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.354
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.123922646).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMTNNM_212557.4 linkc.244C>A p.His82Asn missense_variant Exon 5 of 9 ENST00000339336.9 NP_997722.1 Q6UX39-1F1T0L8
AMTNNM_001286731.2 linkc.241C>A p.His81Asn missense_variant Exon 5 of 9 NP_001273660.1 Q6UX39-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMTNENST00000339336.9 linkc.244C>A p.His82Asn missense_variant Exon 5 of 9 1 NM_212557.4 ENSP00000341013.4 Q6UX39-1
AMTNENST00000504451.1 linkc.241C>A p.His81Asn missense_variant Exon 5 of 9 1 ENSP00000422452.1 Q6UX39-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251184
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461754
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.244C>A (p.H82N) alteration is located in exon 5 (coding exon 4) of the AMTN gene. This alteration results from a C to A substitution at nucleotide position 244, causing the histidine (H) at amino acid position 82 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
8.2
DANN
Benign
0.91
DEOGEN2
Benign
0.0039
T;.
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.034
Sift
Benign
0.059
T;T
Sift4G
Uncertain
0.019
D;D
Polyphen
0.67
P;P
Vest4
0.40
MutPred
0.15
Loss of glycosylation at T79 (P = 0.0522);.;
MVP
0.29
MPC
0.094
ClinPred
0.083
T
GERP RS
2.2
Varity_R
0.056
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs773319021; hg19: chr4-71390628; API