rs28674149

Variant names:

• chr4-70518771-C-G
• rs28674149
• NM_212557.4:c.-7C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-70518771-C-G
• chr4-70518771-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_212557.4(AMTN):​c.-7C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AMTN NM_212557.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 13 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

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.-7C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_997722.1	F1T0L8
	AMTN	NM_212557.4	MANE Select	c.-7C>G		5_prime_UTR	Exon 2 of 9	NP_997722.1	F1T0L8
	AMTN	NM_001286731.2		c.-7C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 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.-7C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000341013.4	Q6UX39-1
	AMTN	ENST00000504451.1	TSL:1	c.-7C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000422452.1	Q6UX39-2
	AMTN	ENST00000339336.9	TSL:1 MANE Select	c.-7C>G		5_prime_UTR	Exon 2 of 9	ENSP00000341013.4	Q6UX39-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 42774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.3
DANN	Benign	0.54
PhyloP100		0.66
PromoterAI		-0.0011	Neutral

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

Other links and lift over

dbSNP: rs28674149; hg19: chr4-71384488;