4-87611030-AGTGTGTGTGTGTGTGT-AGTGTGT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 41 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+95_51+104delTGTGTGTGTG		intron	N/A	NP_055023.2	Q9NZW4
	DMP1-AS1	NR_198971.1		n.367-42507_367-42498delACACACACAC		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+81delGTGTGTGTGT		intron	N/A	ENSP00000498766.1	Q9NZW4
	DMP1-AS1	ENST00000506480.5	TSL:3	n.323-42507_323-42498delACACACACAC		intron	N/A
	DMP1-AS1	ENST00000829286.1		n.357-42507_357-42498delACACACACAC		intron	N/A

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

African (AFR) AF: 0.000336 AC: 6 AN: 17866

American (AMR) AF: 0.0000762 AC: 3 AN: 39368

Ashkenazi Jewish (ASJ) AF: 0.0000493 AC: 1 AN: 20300

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

South Asian (SAS) AF: 0.000380 AC: 26 AN: 68426

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48442

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

European-Non Finnish (NFE) AF: 0.000325 AC: 133 AN: 409842

Other (OTH) AF: 0.000147 AC: 5 AN: 33920

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

African (AFR) AF: 0.000385 AC: 15 AN: 38996

American (AMR) AF: 0.00 AC: 0 AN: 14572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 4984

South Asian (SAS) AF: 0.000444 AC: 2 AN: 4508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000361 AC: 24 AN: 66534

Other (OTH) AF: 0.00 AC: 0 AN: 2018

Alfa AF: 0.00 Hom.: 257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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;