4-87611030-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr4-87611030-A-AGTGTGTGTGTGT
• rs33940466
• NM_014208.3:c.51+93_51+104dupTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014208.3(DSPP):​c.51+93_51+104dupTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 820,828 control chromosomes in the GnomAD database, including 53 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (46 hom., cov: 0)
  • Exomes 𝑓: 0.0067 (7 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2504/145636) while in subpopulation AFR AF= 0.0408 (1590/38960). AF 95% confidence interval is 0.0391. There are 46 homozygotes in gnomad4. There are 1205 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2504 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+93_51+104dupTGTGTGTGTGTG		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.51+71_51+72insGTGTGTGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42498_323-42497insACACACACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2503 AN: 145538 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00180

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.00974

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00670 AC: 4527 AN: 675192 Hom.: 7 AF XY: 0.00676 AC XY: 2445 AN XY: 361910

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.000524

Gnomad4 SAS exome AF: 0.00876

Gnomad4 FIN exome AF: 0.00838

Gnomad4 NFE exome AF: 0.00569

Gnomad4 OTH exome AF: 0.00803

GnomAD4 genome AF: 0.0172 AC: 2504 AN: 145636 Hom.: 46 Cov.: 0 AF XY: 0.0171 AC XY: 1205 AN XY: 70590

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.00666

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00181

Gnomad4 SAS AF: 0.0109

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.00870

Gnomad4 OTH AF: 0.0124

ClinVar

Not reported in ClinVar

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: rs33940466; hg19: chr4-88532182;