4-87612011-TTGTGTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr4-87612011-T-TTG
• rs36228864
• NM_014208.3:c.52-65_52-64dupTG

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_52-64dupTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,064,772 control chromosomes in the GnomAD database, including 139 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (107 hom., cov: 0)
  • Exomes 𝑓: 0.024 (32 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.448

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-T-TTG is Benign according to our data. Variant chr4-87612011-T-TTG is described in ClinVar as [Benign]. Clinvar id is 1244325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.52-65_52-64dupTG		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.52-94_52-93insTG		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-43479_323-43478insCA		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5088 AN: 149950 Hom.: 107 Cov.: 0

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.00551

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0340

GnomAD4 exome AF: 0.0241 AC: 22052 AN: 914714 Hom.: 32 AF XY: 0.0249 AC XY: 11713 AN XY: 471016

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0711

Gnomad4 EAS exome AF: 0.0117

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.00796

Gnomad4 NFE exome AF: 0.0214

Gnomad4 OTH exome AF: 0.0296

GnomAD4 genome AF: 0.0340 AC: 5107 AN: 150058 Hom.: 107 Cov.: 0 AF XY: 0.0333 AC XY: 2438 AN XY: 73222

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.00734

Gnomad4 SAS AF: 0.0430

Gnomad4 FIN AF: 0.00551

Gnomad4 NFE AF: 0.0249

Gnomad4 OTH AF: 0.0336

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 27, 2020

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;