4-87611030-AGTGTGTGTGTGTGTGT-AGT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014208.3(DSPP):​c.51+91_51+104delTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 676,198 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 0 publications found

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]

DSPP Gene-Disease associations (from GenCC):

• deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

  Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• dentinogenesis imperfecta

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dentinogenesis imperfecta type 2

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• dentinogenesis imperfecta type 3

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• dentin dysplasia type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dentin dysplasia type II

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DMP1-AS1 (HGNC:58144):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	NM_014208.3	MANE Select	c.51+91_51+104delTGTGTGTGTGTGTG		intron	N/A	NP_055023.2	Q9NZW4
	DMP1-AS1	NR_198971.1		n.367-42511_367-42498delACACACACACACAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	ENST00000651931.1	MANE Select	c.51+72_51+85delGTGTGTGTGTGTGT		intron	N/A	ENSP00000498766.1	Q9NZW4
	DMP1-AS1	ENST00000506480.5	TSL:3	n.323-42511_323-42498delACACACACACACAC		intron	N/A
	DMP1-AS1	ENST00000829286.1		n.357-42511_357-42498delACACACACACACAC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000887 AC: 6 AN: 676198 Hom.: 0 AF XY: 0.00000828 AC XY: 3 AN XY: 362454

African (AFR) AF: 0.000112 AC: 2 AN: 17860

American (AMR) AF: 0.0000254 AC: 1 AN: 39368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20302

East Asian (EAS) AF: 0.00 AC: 0 AN: 34382

South Asian (SAS) AF: 0.0000292 AC: 2 AN: 68458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3614

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 409852

Other (OTH) AF: 0.0000295 AC: 1 AN: 33920

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs33940466; hg19: chr4-88532182;