4-87611030-AGTGTGTGTGTGT-AGT

Variant names:

• chr4-87611030-AGTGTGTGTGT-A
• rs33940466
• NM_014208.3:c.51+95_51+104delTGTGTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.51+95_51+104delTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 821,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00026 (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 sas. gnomad4 allele frequency = 0.000281 (41/145694) while in subpopulation SAS AF= 0.000444 (2/4508). AF 95% confidence interval is 0.000248. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+95_51+104delTGTGTGTGTG		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+81delGTGTGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42507_323-42498delACACACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.000275 AC: 40 AN: 145596 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000361

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000259 AC: 175 AN: 676160 Hom.: 0 AF XY: 0.000276 AC XY: 100 AN XY: 362426

Gnomad4 AFR exome AF: 0.000336

Gnomad4 AMR exome AF: 0.0000762

Gnomad4 ASJ exome AF: 0.0000493

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000380

Gnomad4 FIN exome AF: 0.0000206

Gnomad4 NFE exome AF: 0.000325

Gnomad4 OTH exome AF: 0.000147

GnomAD4 genome AF: 0.000281 AC: 41 AN: 145694 Hom.: 0 Cov.: 0 AF XY: 0.000241 AC XY: 17 AN XY: 70618

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000444

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000361

Gnomad4 OTH AF: 0.00

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;