4-87611030-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr4-87611030-A-AGTGTGTGTGTGTGT
• rs33940466
• NM_014208.3:c.51+91_51+104dupTGTGTGTGTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.51+91_51+104dupTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00021 (1 hom.)
  • Failed GnomAD Quality Control
• 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 = 0.000597 (87/145688) while in subpopulation AFR AF= 0.00138 (54/38990). AF 95% confidence interval is 0.00109. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 87 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+91_51+104dupTGTGTGTGTGTGTG		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+72insGTGTGTGTGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42498_323-42497insACACACACACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 87 AN: 145590 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000893

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000600

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000240

Gnomad OTH AF: 0.000500

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000211 AC: 143 AN: 676138 Hom.: 1 AF XY: 0.000204 AC XY: 74 AN XY: 362420

Gnomad4 AFR exome AF: 0.00190

Gnomad4 AMR exome AF: 0.000229

Gnomad4 ASJ exome AF: 0.000296

Gnomad4 EAS exome AF: 0.0000873

Gnomad4 SAS exome AF: 0.000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000597 AC: 87 AN: 145688 Hom.: 0 Cov.: 0 AF XY: 0.000581 AC XY: 41 AN XY: 70610

Gnomad4 AFR AF: 0.00138

Gnomad4 AMR AF: 0.000892

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000602

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000240

Gnomad4 OTH AF: 0.000496

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;