4-87612011-TTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTG

Variant names:

• chr4-87612011-TTGTG-T
• rs36228864
• NM_014208.3:c.52-67_52-64delTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.52-67_52-64delTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,065,454 control chromosomes in the GnomAD database, including 294 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (205 hom., cov: 0)
  • Exomes 𝑓: 0.016 (89 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-TTGTG-T is Benign according to our data. Variant chr4-87612011-TTGTG-T is described in ClinVar as [Benign]. Clinvar id is 1251915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.52-67_52-64delTGTG		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_52-90delTGTG		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-43482_323-43479delCACA		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5775 AN: 149940 Hom.: 204 Cov.: 0

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.00226

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00725

Gnomad EAS AF: 0.00594

Gnomad SAS AF: 0.0440

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0164 AC: 15019 AN: 915408 Hom.: 89 AF XY: 0.0170 AC XY: 8022 AN XY: 471460

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.00730

Gnomad4 EAS exome AF: 0.00433

Gnomad4 SAS exome AF: 0.0381

Gnomad4 FIN exome AF: 0.0347

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.0385 AC: 5782 AN: 150046 Hom.: 205 Cov.: 0 AF XY: 0.0395 AC XY: 2889 AN XY: 73224

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00725

Gnomad4 EAS AF: 0.00595

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.0303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs36228864; hg19: chr4-88533163;