4-87611030-AGTGTGTGTGTGT-AGTGT

Variant names:

• chr4-87611030-AGTGTGTGT-A
• rs33940466
• NM_014208.3:c.51+97_51+104delTGTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.51+97_51+104delTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 821,828 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0037 (4 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 sas. gnomad4 allele frequency = 0.0021 (306/145692) while in subpopulation SAS AF= 0.0226 (102/4508). AF 95% confidence interval is 0.0191. There are 1 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+97_51+104delTGTGTGTG		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+79delGTGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42505_323-42498delACACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 304 AN: 145594 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000926

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000587

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.00200

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00183

Gnomad OTH AF: 0.00300

GnomAD4 exome AF: 0.00371 AC: 2507 AN: 676136 Hom.: 4 AF XY: 0.00462 AC XY: 1673 AN XY: 362420

Gnomad4 AFR exome AF: 0.000952

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.000175

Gnomad4 SAS exome AF: 0.0213

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00185

Gnomad4 OTH exome AF: 0.00313

GnomAD4 genome AF: 0.00210 AC: 306 AN: 145692 Hom.: 1 Cov.: 0 AF XY: 0.00252 AC XY: 178 AN XY: 70618

Gnomad4 AFR AF: 0.000923

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000587

Gnomad4 EAS AF: 0.000201

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.00200

Gnomad4 NFE AF: 0.00183

Gnomad4 OTH AF: 0.00297

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;