chr4-87612011-TTG-T

Position:

• chr4-87612011-TTG-T

Variant summary

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

The NM_014208.3(DSPP):​c.52-65_52-64del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 1,039,370 control chromosomes in the GnomAD database, including 1,075 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (940 hom., cov: 0)
  • Exomes 𝑓: 0.042 (135 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.232

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 -10 ACMG points.

• BP6: Variant 4-87612011-TTG-T is Benign according to our data. Variant chr4-87612011-TTG-T is described in ClinVar as [Benign]. Clinvar id is 1272159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSPP	NM_014208.3	c.52-65_52-64del		intron_variant		ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.52-65_52-64del		intron_variant			NM_014208.3	P1
	ENST00000506480.5	n.323-43480_323-43479del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11321 AN: 149844 Hom.: 942 Cov.: 0

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0113

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0656

GnomAD4 exome AF: 0.0419 AC: 37281 AN: 889418 Hom.: 135 AF XY: 0.0413 AC XY: 18860 AN XY: 457012

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0510

Gnomad4 ASJ exome AF: 0.0652

Gnomad4 EAS exome AF: 0.0531

Gnomad4 SAS exome AF: 0.0334

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0340

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.0756 AC: 11341 AN: 149952 Hom.: 940 Cov.: 0 AF XY: 0.0744 AC XY: 5443 AN XY: 73174

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0288

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0324

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0644

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

Jul 19, 2020

- -

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;