4-87611030-AGT-A

Variant names:

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

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+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

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:58144):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+103_51+104delTG		intron_variant	Intron 2 of 4	ENST00000651931.1	NP_055023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1	c.51+72_51+73delGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42499_323-42498delAC		intron_variant	Intron 3 of 3	3

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

Gnomad4 AFR exome AF: 0.0997

Gnomad4 AMR exome AF: 0.0794

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.148

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

Gnomad4 AFR AF: 0.0975

Gnomad4 AMR AF: 0.0876

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs33940466; hg19: chr4-88532182;