4-87612011-TTGTGTGTGTGTGTGTGTG-TTGTGTGTGTG

Variant names:

• chr4-87612011-TTGTGTGTG-T
• rs36228864
• NM_014208.3:c.52-71_52-64delTGTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.52-71_52-64delTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,063,666 control chromosomes in the GnomAD database, including 77,975 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13921 hom., cov: 0)
  • Exomes 𝑓: 0.44 (64054 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

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:58144):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-87612011-TTGTGTGTG-T is Benign according to our data. Variant chr4-87612011-TTGTGTGTG-T is described in ClinVar as [Benign]. Clinvar id is 1235086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.52-71_52-64delTGTGTGTG		intron_variant	Intron 2 of 4	ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.52-93_52-86delTGTGTGTG		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-43486_323-43479delCACACACA		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 61272 AN: 149830 Hom.: 13916 Cov.: 0

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.441 AC: 402753 AN: 913728 Hom.: 64054 AF XY: 0.439 AC XY: 206631 AN XY: 470568

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.409 AC: 61292 AN: 149938 Hom.: 13921 Cov.: 0 AF XY: 0.407 AC XY: 29798 AN XY: 73162

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.441

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36228864; hg19: chr4-88533163;