4-87611030-AGTGT-A

Position:

• chr4-87611030-AGTGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014208.3(DSPP):​c.51+101_51+104delTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 814,044 control chromosomes in the GnomAD database, including 163 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (131 hom., cov: 0)
  • Exomes 𝑓: 0.036 (32 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257

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]

ENSG00000249001 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-87611030-AGTGT-A is Benign according to our data. Variant chr4-87611030-AGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1298011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+101_51+104delTGTG		intron_variant		ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.51+101_51+104delTGTG		intron_variant			NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42501_323-42498delACAC		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5677 AN: 145566 Hom.: 131 Cov.: 0

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00941

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0340

GnomAD4 exome AF: 0.0360 AC: 24095 AN: 668380 Hom.: 32 AF XY: 0.0372 AC XY: 13312 AN XY: 357786

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.0448

Gnomad4 SAS exome AF: 0.0517

Gnomad4 FIN exome AF: 0.0239

Gnomad4 NFE exome AF: 0.0336

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0390 AC: 5687 AN: 145664 Hom.: 131 Cov.: 0 AF XY: 0.0380 AC XY: 2685 AN XY: 70594

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.00923

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0314

Gnomad4 OTH AF: 0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs33940466; hg19: chr4-88532182;