NM_016519.6:c.281A>C

Variant names:

• chr4-70599633-A-C
• rs866630412
• NM_016519.6:c.281A>C

Variant summary

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

The NM_016519.6(AMBN):​c.281A>C​(p.His94Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AMBN NM_016519.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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.281A>C	p.His94Pro	missense_variant	Exon 5 of 13	ENST00000322937.10	NP_057603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10	c.281A>C	p.His94Pro	missense_variant	Exon 5 of 13	1	NM_016519.6	ENSP00000313809.6
AMBN	ENST00000449493.2	c.281A>C	p.His94Pro	missense_variant	Exon 5 of 13	5		ENSP00000391234.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.23	T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.6	D;.;D
REVEL	Benign	0.23
Sift	Uncertain	0.012	D;.;T
Sift4G	Benign	0.30	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.70
MutPred		0.55		Gain of glycosylation at Y99 (P = 2e-04);Gain of glycosylation at Y99 (P = 2e-04);Gain of glycosylation at Y99 (P = 2e-04);
MVP		0.63
MPC		0.24
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.67
gMVP		0.60

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

Other links and lift over

dbSNP: rs866630412; hg19: chr4-71465350;