4-87611030-A-AGTGTGT

Variant names:

• chr4-87611030-A-AGTGTGT
• rs33940466
• NM_014208.3:c.51+99_51+104dupTGTGTG

Variant summary

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

The NM_014208.3(DSPP):​c.51+99_51+104dupTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 818,428 control chromosomes in the GnomAD database, including 182 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (133 hom., cov: 0)
  • Exomes 𝑓: 0.035 (49 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-AGTGTGT is Benign according to our data. Variant chr4-87611030-A-AGTGTGT is described in ClinVar as [Benign]. Clinvar id is 1276925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSPP	NM_014208.3	c.51+99_51+104dupTGTGTG		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+72insGTGTGT		intron_variant	Intron 2 of 4		NM_014208.3	ENSP00000498766.1
ENSG00000249001	ENST00000506480.5	n.323-42498_323-42497insACACAC		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5573 AN: 145524 Hom.: 132 Cov.: 0

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0269

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0370

GnomAD4 exome AF: 0.0351 AC: 23586 AN: 672806 Hom.: 49 AF XY: 0.0367 AC XY: 13218 AN XY: 360560

Gnomad4 AFR exome AF: 0.0402

Gnomad4 AMR exome AF: 0.0804

Gnomad4 ASJ exome AF: 0.0356

Gnomad4 EAS exome AF: 0.0341

Gnomad4 SAS exome AF: 0.0682

Gnomad4 FIN exome AF: 0.0540

Gnomad4 NFE exome AF: 0.0228

Gnomad4 OTH exome AF: 0.0338

GnomAD4 genome AF: 0.0383 AC: 5579 AN: 145622 Hom.: 133 Cov.: 0 AF XY: 0.0416 AC XY: 2934 AN XY: 70582

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.0373

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0755

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;