4-87611030-A-AGT

Variant names:

• chr4-87611030-A-AGT
• rs33940466
• NM_014208.3:c.51+103_51+104dupTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014208.3(DSPP):​c.51+103_51+104dupTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 797,612 control chromosomes in the GnomAD database, including 2,661 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2384 hom., cov: 0)
  • Exomes 𝑓: 0.18 (277 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257
• 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 -10 ACMG points.

• BP6: Variant 4-87611030-A-AGT is Benign according to our data. Variant chr4-87611030-A-AGT is described in ClinVar as Benign. ClinVar VariationId is 1269186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

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+103_51+104dupTG		intron	N/A	NP_055023.2	Q9NZW4
	DMP1-AS1	NR_198971.1		n.367-42499_367-42498dupAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSPP	ENST00000651931.1	MANE Select	c.51+71_51+72insGT		intron	N/A	ENSP00000498766.1	Q9NZW4
	DMP1-AS1	ENST00000506480.5	TSL:3	n.323-42498_323-42497insAC		intron	N/A
	DMP1-AS1	ENST00000829286.1		n.357-42498_357-42497insAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.184 AC: 26686 AN: 145274 Hom.: 2387 Cov.: 0

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.176 AC: 114888 AN: 652246 Hom.: 277 AF XY: 0.176 AC XY: 61541 AN XY: 350124

African (AFR) AF: 0.171 AC: 2993 AN: 17544

American (AMR) AF: 0.186 AC: 6811 AN: 36668

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 3219 AN: 19774

East Asian (EAS) AF: 0.0582 AC: 1965 AN: 33754

South Asian (SAS) AF: 0.116 AC: 7806 AN: 67162

European-Finnish (FIN) AF: 0.213 AC: 9984 AN: 46768

Middle Eastern (MID) AF: 0.191 AC: 675 AN: 3526

European-Non Finnish (NFE) AF: 0.192 AC: 75511 AN: 394284

Other (OTH) AF: 0.181 AC: 5924 AN: 32766

GnomAD4 genome AF: 0.184 AC: 26696 AN: 145366 Hom.: 2384 Cov.: 0 AF XY: 0.178 AC XY: 12523 AN XY: 70462

African (AFR) AF: 0.202 AC: 7875 AN: 38940

American (AMR) AF: 0.140 AC: 2032 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 533 AN: 3404

East Asian (EAS) AF: 0.0413 AC: 206 AN: 4982

South Asian (SAS) AF: 0.0979 AC: 440 AN: 4496

European-Finnish (FIN) AF: 0.194 AC: 1829 AN: 9440

Middle Eastern (MID) AF: 0.246 AC: 70 AN: 284

European-Non Finnish (NFE) AF: 0.199 AC: 13225 AN: 66396

Other (OTH) AF: 0.181 AC: 364 AN: 2014

Alfa AF: 0.206 Hom.: 257

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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;