4-87611030-AGTGTGTGTGTGT-A

Variant names:

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

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+104delTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 821,884 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0067 (10 hom., cov: 0)
  • Exomes 𝑓: 0.00091 (0 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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 = 0.00666 (970/145690) while in subpopulation AFR AF= 0.0227 (885/38992). AF 95% confidence interval is 0.0215. There are 10 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 970 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+93_51+104delTGTGTGTGTGTG		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+72_51+83delGTGTGTGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42509_323-42498delACACACACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 972 AN: 145592 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00447

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000443

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000751

Gnomad OTH AF: 0.00650

GnomAD4 exome AF: 0.000912 AC: 617 AN: 676194 Hom.: 0 AF XY: 0.000737 AC XY: 267 AN XY: 362450

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.00178

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000438

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000903

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00666 AC: 970 AN: 145690 Hom.: 10 Cov.: 0 AF XY: 0.00656 AC XY: 463 AN XY: 70614

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.00446

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000444

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000751

Gnomad4 OTH AF: 0.00644

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;