4-87611030-A-AGT

Position:

• chr4-87611030-A-AGT

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+103_51+104dupTG		intron_variant		ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.51+103_51+104dupTG		intron_variant			NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42499_323-42498dupAC		intron_variant		3

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

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0582

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.181

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

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

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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: rs33940466; hg19: chr4-88532182;