GeneBe

rs33940466

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014208.3(DSPP):​c.51+89_51+104delTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 676,204 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DSPP
NM_014208.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.272

Publications

0 publications found
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]
DSPP Gene-Disease associations (from GenCC):
  • deafness, autosomal dominant 39, with dentinogenesis imperfecta 1
    Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
  • dentinogenesis imperfecta
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • dentinogenesis imperfecta type 2
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
  • dentinogenesis imperfecta type 3
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • dentin dysplasia type I
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • dentin dysplasia type II
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DSPP
NM_014208.3
MANE Select
c.51+89_51+104delTGTGTGTGTGTGTGTG
intron
N/ANP_055023.2Q9NZW4
DMP1-AS1
NR_198971.1
n.367-42513_367-42498delACACACACACACACAC
intron
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DSPP
ENST00000651931.1
MANE Select
c.51+72_51+87delGTGTGTGTGTGTGTGT
intron
N/AENSP00000498766.1Q9NZW4
DMP1-AS1
ENST00000506480.5
TSL:3
n.323-42513_323-42498delACACACACACACACAC
intron
N/A
DMP1-AS1
ENST00000829286.1
n.357-42513_357-42498delACACACACACACACAC
intron
N/A

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
145596
Hom.:
0
Cov.:
0
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000148
AC:
1
AN:
676204
Hom.:
0
AF XY:
0.00000276
AC XY:
1
AN XY:
362454
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
17866
American (AMR)
AF:
0.00
AC:
0
AN:
39368
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20302
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34382
South Asian (SAS)
AF:
0.00
AC:
0
AN:
68458
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48442
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3614
European-Non Finnish (NFE)
AF:
0.00000244
AC:
1
AN:
409852
Other (OTH)
AF:
0.00
AC:
0
AN:
33920
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
145596
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
70510
African (AFR)
AF:
0.00
AC:
0
AN:
38886
American (AMR)
AF:
0.00
AC:
0
AN:
14554
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3406
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4998
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4510
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9498
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
66544
Other (OTH)
AF:
0.00
AC:
0
AN:
2000

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs33940466; hg19: chr4-88532182; API