Genetic Variant DSPP:c.51+89_51+104dupTGTGTGTGTGTGTGTG (chr4-87611030-A-AGTGTGTGTGTGTGTGT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014208.3(DSPP):c.51+89_51+104dupTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.000089 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSPP
NM_014208.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.257

Publications

3 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: Orphanet, G2P
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

DSPP links:

DMP1-AS1 (HGNC:58144):

DMP1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014208.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 13 AD,Unknown gene.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	NM_014208.3	MANE Select	c.51+89_51+104dupTGTGTGTGTGTGTGTG		intron	N/A	NP_055023.2	Q9NZW4
	DMP1-AS1	NR_198971.1		n.367-42513_367-42498dupACACACACACACACAC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSPP	ENST00000651931.1	MANE Select	c.51+71_51+72insGTGTGTGTGTGTGTGT	intron	N/A	ENSP00000498766.1	Q9NZW4
DMP1-AS1	ENST00000506480.5	TSL:3	n.323-42498_323-42497insACACACACACACACAC	intron	N/A
DMP1-AS1	ENST00000829286.1		n.357-42498_357-42497insACACACACACACACAC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000893

AC:

AN:

145594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000154

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:

0.000105

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000192

AC:

AN:

676188

Hom.:

AF XY:

0.0000166

AC XY:

AN XY:

362450

show subpopulations

African (AFR)

AF:

0.0000560

AC:

AN:

17862

American (AMR)

AF:

0.0000254

AC:

AN:

39368

Ashkenazi Jewish (ASJ)

AF:

0.0000493

AC:

AN:

20302

East Asian (EAS)

AF:

0.00

AC:

AN:

34382

South Asian (SAS)

AF:

0.00

AC:

AN:

68458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3614

European-Non Finnish (NFE)

AF:

0.0000220

AC:

AN:

409840

Other (OTH)

AF:

0.0000295

AC:

AN:

33920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.0000893

AC:

AN:

145594

Hom.:

Cov.:

AF XY:

0.0000709

AC XY:

AN XY:

70510

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

38884

American (AMR)

AF:

0.00

AC:

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4998

South Asian (SAS)

AF:

0.00

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000105

AC:

AN:

66544

Other (OTH)

AF:

0.00

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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4-87611030-AGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over