4-87611030-A-AGTGT

Variant names:

• chr4-87611030-A-AGTGT
• rs33940466
• NM_014208.3:c.51+101_51+104dupTGTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014208.3(DSPP):​c.51+101_51+104dupTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 813,642 control chromosomes in the GnomAD database, including 8,400 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7054 hom., cov: 0)
  • Exomes 𝑓: 0.23 (1346 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-A-AGTGT is Benign according to our data. Variant chr4-87611030-A-AGTGT is described in ClinVar as [Benign]. Clinvar id is 1285915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+101_51+104dupTGTG		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+71_51+72insGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42498_323-42497insACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 43630 AN: 145348 Hom.: 7050 Cov.: 0

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.234 AC: 156143 AN: 668194 Hom.: 1346 AF XY: 0.231 AC XY: 82584 AN XY: 358086

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.300 AC: 43651 AN: 145448 Hom.: 7054 Cov.: 0 AF XY: 0.299 AC XY: 21090 AN XY: 70470

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.311

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 08, 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

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;