Variant NM_014208.3:c.136-29T>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014208.3(DSPP):c.136-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,612,380 control chromosomes in the GnomAD database, including 67,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.23 ( 4421 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62912 hom. )

Consequence

DSPP
NM_014208.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.08

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 links:

ENSG00000249001 (HGNC:58144):

ENSG00000249001 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-87612293-T-C is Benign according to our data. Variant chr4-87612293-T-C is described in ClinVar as [Benign]. Clinvar id is 260355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3 link	c.136-29T>C		intron_variant	Intron 3 of 4	ENST00000651931.1	NP_055023.2	Q9NZW4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 link	c.136-29T>C		intron_variant	Intron 3 of 4		NM_014208.3	ENSP00000498766.1		Q9NZW4
ENSG00000249001	ENST00000506480.5 link	n.323-43760A>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34397

AN:

151976

Hom.:

4413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0964

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.252

AC:

62326

AN:

246932

Hom.:

8392

AF XY:

0.262

AC XY:

35069

AN XY:

133940

show subpopulations

Gnomad AFR exome

AF:

0.0858

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.289

AC:

422695

AN:

1460286

Hom.:

62912

Cov.:

AF XY:

0.291

AC XY:

211044

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.0867

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.226

AC:

34412

AN:

152094

Hom.:

4421

Cov.:

AF XY:

0.223

AC XY:

16600

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0965

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.267

Hom.:

1514

Bravo

AF:

0.213

Asia WGS

AF:

0.276

AC:

960

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.90

CADD

Benign

1.8

DANN

Benign

0.47

BranchPoint Hunter

2.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over