4-87612011-TTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTG

Variant names:

• chr4-87612011-TTGTGTG-T
• rs36228864
• NM_014208.3:c.52-69_52-64delTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.52-69_52-64delTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,060,466 control chromosomes in the GnomAD database, including 2,674 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (713 hom., cov: 0)
  • Exomes 𝑓: 0.083 (1961 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-TTGTGTG-T is Benign according to our data. Variant chr4-87612011-TTGTGTG-T is described in ClinVar as [Benign]. Clinvar id is 1270839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.52-69_52-64delTGTGTG		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_52-88delTGTGTG		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-43484_323-43479delCACACA		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11449 AN: 149912 Hom.: 714 Cov.: 0

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.00340

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0792

GnomAD4 exome AF: 0.0834 AC: 75951 AN: 910446 Hom.: 1961 AF XY: 0.0841 AC XY: 39426 AN XY: 469026

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0851

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.0943

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0681

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0763 AC: 11454 AN: 150020 Hom.: 713 Cov.: 0 AF XY: 0.0797 AC XY: 5835 AN XY: 73208

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.0706

Gnomad4 OTH AF: 0.0803

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;