4-87612011-TTGTGTGTGTGTGTGTGTG-TTGTGTGTG

Variant names:

• chr4-87612011-TTGTGTGTGTG-T
• rs36228864
• NM_014208.3:c.52-73_52-64delTGTGTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.52-73_52-64delTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,007,858 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (1 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 nfe. gnomad4 allele frequency = 0.000267 (40/149972) while in subpopulation NFE AF= 0.000372 (25/67266). AF 95% confidence interval is 0.000258. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.52-73_52-64delTGTGTGTGTG		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.52-93_52-84delTGTGTGTGTG		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-43488_323-43479delCACACACACA		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.000267 AC: 40 AN: 149864 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000970

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000372

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0133 AC: 11385 AN: 857886 Hom.: 1 AF XY: 0.0131 AC XY: 5766 AN XY: 440680

Gnomad4 AFR exome AF: 0.00246

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.00989

Gnomad4 EAS exome AF: 0.00545

Gnomad4 SAS exome AF: 0.00729

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.000267 AC: 40 AN: 149972 Hom.: 0 Cov.: 0 AF XY: 0.000273 AC XY: 20 AN XY: 73156

Gnomad4 AFR AF: 0.000220

Gnomad4 AMR AF: 0.000199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000970

Gnomad4 NFE AF: 0.000372

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: rs36228864; hg19: chr4-88533163;