4-87612289-T-C

Variant names:

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.136-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,611,870 control chromosomes in the GnomAD database, including 227,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16972 hom., cov: 32)

Exomes 𝑓: 0.53 ( 211010 hom. )

Consequence

DSPP
NM_014208.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.387

Publications

12 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 (BayesDel_noAF=-0.83).

BP6

Variant 4-87612289-T-C is Benign according to our data. Variant chr4-87612289-T-C is described in ClinVar as [Benign]. Clinvar id is 260356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.136-33T>C		intron_variant	Intron 3 of 4	ENST00000651931.1	NP_055023.2	Q9NZW4
DMP1-AS1	NR_198971.1 link	n.367-43756A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.136-33T>C		intron_variant	Intron 3 of 4		NM_014208.3	ENSP00000498766.1		Q9NZW4

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68404

AN:

151862

Hom.:

16963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.676

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.481

GnomAD2 exomes

AF:

0.522

AC:

128705

AN:

246538

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.536

GnomAD4 exome

AF:

0.535

AC:

780415

AN:

1459890

Hom.:

211010

Cov.:

AF XY:

0.533

AC XY:

387371

AN XY:

726122

show subpopulations

African (AFR)

AF:

0.211

AC:

7062

AN:

33454

American (AMR)

AF:

0.543

AC:

24160

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

12403

AN:

26114

East Asian (EAS)

AF:

0.633

AC:

25089

AN:

39654

South Asian (SAS)

AF:

0.482

AC:

41474

AN:

86080

European-Finnish (FIN)

AF:

0.535

AC:

28526

AN:

53334

Middle Eastern (MID)

AF:

0.534

AC:

3075

AN:

5762

European-Non Finnish (NFE)

AF:

0.547

AC:

607260

AN:

1110690

Other (OTH)

AF:

0.520

AC:

31366

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

19990

39980

59969

79959

99949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.450

AC:

68435

AN:

151980

Hom.:

16972

Cov.:

AF XY:

0.451

AC XY:

33471

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.220

AC:

9134

AN:

41492

American (AMR)

AF:

0.493

AC:

7531

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1625

AN:

3470

East Asian (EAS)

AF:

0.677

AC:

3497

AN:

5164

South Asian (SAS)

AF:

0.486

AC:

2343

AN:

4822

European-Finnish (FIN)

AF:

0.532

AC:

5607

AN:

10544

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.545

AC:

37033

AN:

67902

Other (OTH)

AF:

0.488

AC:

1030

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1800

3600

5401

7201

9001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.500

Hom.:

18468

Bravo

AF:

0.442

Asia WGS

AF:

0.581

AC:

2023

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

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:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dentinogenesis imperfecta type 3

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Denticles

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dentinogenesis imperfecta type 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

(source)

DANN

Benign

0.70

PhyloP100

-0.39

Mutation Taster

=100/0

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

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4-87612289-T-C

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