4-70601529-C-G

Variant names:

• chr4-70601529-C-G
• NM_016519.6:c.406C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016519.6(AMBN):​c.406C>G​(p.Gln136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AMBN NM_016519.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMBN	NM_016519.6	c.406C>G	p.Gln136Glu	missense_variant	Exon 6 of 13	ENST00000322937.10	NP_057603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10	c.406C>G	p.Gln136Glu	missense_variant	Exon 6 of 13	1	NM_016519.6	ENSP00000313809.6
AMBN	ENST00000449493.2	c.361C>G	p.Gln121Glu	missense_variant	Exon 6 of 13	5		ENSP00000391234.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.54
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.45	T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.0	N;.;N
REVEL	Benign	0.16
Sift	Benign	0.12	T;.;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.37
MutPred		0.76		Loss of glycosylation at T133 (P = 0.0294);Loss of glycosylation at T133 (P = 0.0294);.;
MVP		0.38
MPC		0.062
ClinPred		0.087	T
GERP RS		4.8
Varity_R		0.061
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-71467246;