4-87610924-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_014208.3(DSPP):​c.16T>G​(p.Tyr6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

DSPP
NM_014208.3 missense

Scores

4
8
5

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.15
Variant links:
Genes affected
DSPP (HGNC:3054): (dentin sialophosphoprotein) This gene encodes a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins. The encoded preproprotein is secreted by odontoblasts and proteolytically processed to generate two principal proteins of the dentin extracellular matrix of the tooth, dentin sialoprotein and dentin phosphoprotein. These two protein products may play distinct but related roles in dentin mineralization. Mutations in this gene are associated with dentinogenesis imperfecta and dentin dysplasia. This gene is present in a gene cluster on chromosome 4. Allelic differences due to repeat polymorphisms have been found for this gene. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867
PP5
Variant 4-87610924-T-G is Pathogenic according to our data. Variant chr4-87610924-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 16857.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-87610924-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DSPPNM_014208.3 linkc.16T>G p.Tyr6Asp missense_variant Exon 2 of 5 ENST00000651931.1 NP_055023.2 Q9NZW4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DSPPENST00000651931.1 linkc.16T>G p.Tyr6Asp missense_variant Exon 2 of 5 NM_014208.3 ENSP00000498766.1 Q9NZW4
ENSG00000249001ENST00000506480.5 linkn.323-42391A>C intron_variant Intron 3 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Denticles Pathogenic:1
Oct 01, 2002
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.42
T
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
0.73
D
MutationAssessor
Benign
1.9
L
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.63
Sift4G
Uncertain
0.012
D
Polyphen
0.99
D
Vest4
0.82
MutPred
0.51
Gain of disorder (P = 0.0231);
MVP
0.91
ClinPred
0.89
D
GERP RS
3.7
Varity_R
0.53
gMVP
0.55

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121912988; hg19: chr4-88532076; API