rs13131936

chr4-87612293-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4421 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62912 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: 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/exons	MANE	UniProt
DSPP	NM_014208.3	c.136-29T>C		intron_variant		ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.136-29T>C		intron_variant			NM_014208.3	P1
	ENST00000506480.5	n.323-43760A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34397 AN: 151976 Hom.: 4413 Cov.: 32

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

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.: 61 AF XY: 0.291 AC XY: 211044 AN XY: 726374

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.: 32 AF XY: 0.223 AC XY: 16600 AN XY: 74352

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.47

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

Other links and lift over

dbSNP: rs13131936; hg19: chr4-88533445; COSMIC: COSV56807606;