Variant 4-87612289-T-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.136-33T>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

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DSPP	NM_014208.3 linkuse as main transcript	c.136-33T>C		intron_variant		ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 linkuse as main transcript	c.136-33T>C		intron_variant			NM_014208.3	ENSP00000498766	P1
	ENST00000506480.5 linkuse as main transcript	n.323-43756A>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.522

AC:

128705

AN:

246538

Hom.:

34540

AF XY:

0.522

AC XY:

69785

AN XY:

133722

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 SAS exome

AF:

0.485

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

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.535

Gnomad4 NFE exome

AF:

0.547

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.450

AC:

68435

AN:

151980

Hom.:

16972

Cov.:

AF XY:

0.451

AC XY:

33471

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.516

Hom.:

14080

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Dentinogenesis imperfecta type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Denticles

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Dentinogenesis imperfecta type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

DANN

Benign

0.70

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