NM_014208.3:c.51+103_51+104delTG

Variant names:

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

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+104delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 811,470 control chromosomes in the GnomAD database, including 1,756 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1278 hom., cov: 0)
  • Exomes 𝑓: 0.14 (478 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-AGT-A is Benign according to our data. Variant chr4-87611030-AGT-A is described in ClinVar as Benign. ClinVar VariationId is 1281125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 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+104delTG		intron	N/A	NP_055023.2	Q9NZW4
	DMP1-AS1	NR_198971.1		n.367-42499_367-42498delAC		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+73delGT		intron	N/A	ENSP00000498766.1	Q9NZW4
	DMP1-AS1	ENST00000506480.5	TSL:3	n.323-42499_323-42498delAC		intron	N/A
	DMP1-AS1	ENST00000829286.1		n.357-42499_357-42498delAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18041 AN: 145456 Hom.: 1280 Cov.: 0

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.140 AC: 93366 AN: 665916 Hom.: 478 AF XY: 0.148 AC XY: 52788 AN XY: 356838

African (AFR) AF: 0.0997 AC: 1760 AN: 17660

American (AMR) AF: 0.0794 AC: 3079 AN: 38792

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 4731 AN: 20052

East Asian (EAS) AF: 0.294 AC: 9718 AN: 33040

South Asian (SAS) AF: 0.255 AC: 17031 AN: 66878

European-Finnish (FIN) AF: 0.120 AC: 5747 AN: 47862

Middle Eastern (MID) AF: 0.193 AC: 686 AN: 3560

European-Non Finnish (NFE) AF: 0.113 AC: 45688 AN: 404698

Other (OTH) AF: 0.148 AC: 4926 AN: 33374

GnomAD4 genome AF: 0.124 AC: 18044 AN: 145554 Hom.: 1278 Cov.: 0 AF XY: 0.128 AC XY: 9048 AN XY: 70550

African (AFR) AF: 0.0975 AC: 3800 AN: 38972

American (AMR) AF: 0.0876 AC: 1275 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 882 AN: 3400

East Asian (EAS) AF: 0.310 AC: 1543 AN: 4978

South Asian (SAS) AF: 0.296 AC: 1332 AN: 4504

European-Finnish (FIN) AF: 0.114 AC: 1077 AN: 9476

Middle Eastern (MID) AF: 0.178 AC: 51 AN: 286

European-Non Finnish (NFE) AF: 0.115 AC: 7665 AN: 66482

Other (OTH) AF: 0.133 AC: 267 AN: 2014

Alfa AF: 0.113 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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs33940466; hg19: chr4-88532182;