rs3750025

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014208.3(DSPP):c.727G>A(p.Asp243Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,614,080 control chromosomes in the GnomAD database, including 3,226 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 391 hom., cov: 32)

Exomes 𝑓: 0.032 ( 2835 hom. )

Consequence

DSPP
NM_014208.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.40

Publications

23 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, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
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:

ENSG00000249001 (HGNC:58144):

ENSG00000249001 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008893698).

BP6

Variant 4-87612913-G-A is Benign according to our data. Variant chr4-87612913-G-A is described in ClinVar as Benign. ClinVar VariationId is 197292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.727G>A	p.Asp243Asn	missense_variant	Exon 4 of 5	ENST00000651931.1	NP_055023.2	Q9NZW4
DMP1-AS1	NR_198971.1 link	n.367-44380C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.727G>A	p.Asp243Asn	missense_variant	Exon 4 of 5		NM_014208.3	ENSP00000498766.1		Q9NZW4

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5391

AN:

152102

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.0562

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0421

GnomAD2 exomes

AF:

0.0583

AC:

14549

AN:

249448

AF XY:

0.0534

show subpopulations

Gnomad AFR exome

AF:

0.0230

Gnomad AMR exome

AF:

0.0931

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0446

GnomAD4 exome

AF:

0.0322

AC:

47120

AN:

1461860

Hom.:

2835

Cov.:

AF XY:

0.0318

AC XY:

23149

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.0240

AC:

805

AN:

33480

American (AMR)

AF:

0.0859

AC:

3843

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

674

AN:

26134

East Asian (EAS)

AF:

0.314

AC:

12484

AN:

39700

South Asian (SAS)

AF:

0.0418

AC:

3601

AN:

86248

European-Finnish (FIN)

AF:

0.0219

AC:

1169

AN:

53418

Middle Eastern (MID)

AF:

0.0179

AC:

103

AN:

5768

European-Non Finnish (NFE)

AF:

0.0195

AC:

21677

AN:

1111998

Other (OTH)

AF:

0.0458

AC:

2764

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2938

5876

8814

11752

14690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1094

2188

3282

4376

5470

<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:

0.0355

AC:

5400

AN:

152220

Hom.:

391

Cov.:

AF XY:

0.0375

AC XY:

2790

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0225

AC:

935

AN:

41530

American (AMR)

AF:

0.0413

AC:

631

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

3472

East Asian (EAS)

AF:

0.357

AC:

1843

AN:

5166

South Asian (SAS)

AF:

0.0553

AC:

266

AN:

4814

European-Finnish (FIN)

AF:

0.0233

AC:

247

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0190

AC:

1289

AN:

68004

Other (OTH)

AF:

0.0431

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

235

471

706

942

1177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0297

Hom.:

940

Bravo

AF:

0.0406

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.0227

AC:

ESP6500EA

AF:

0.0208

AC:

174

ExAC

AF:

0.0557

AC:

6742

Asia WGS

AF:

0.166

AC:

576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Nov 28, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 23018043, 18797159) -

Feb 13, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.098

Eigen

Benign

0.095

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.4

MutationAssessor

Benign

0.63

PhyloP100

3.4

PROVEAN

Benign

-0.94

REVEL

Uncertain

0.34

Sift4G

Benign

0.37

Polyphen

0.99

Vest4

0.099

ClinPred

0.033

GERP RS

3.7

Varity_R

0.17

gMVP

0.020

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over