chr4-87611029-TAGTGTGTG-T

Position:

• chr4-87611029-TAGTGTGTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014208.3(DSPP):​c.51+71_51+78del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,031,126 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 0)
  • Exomes 𝑓: 0.00078 (6 hom.)
• Consequence: DSPP NM_014208.3 intron
• Clinical Significance: Likely 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-87611029-TAGTGTGTG-T is Benign according to our data. Variant chr4-87611029-TAGTGTGTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1019/79700) while in subpopulation AFR AF= 0.0502 (974/19420). AF 95% confidence interval is 0.0475. There are 19 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1019 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSPP	NM_014208.3	c.51+71_51+78del		intron_variant		ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.51+71_51+78del		intron_variant			NM_014208.3	P1
	ENST00000506480.5	n.323-42504_323-42497del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1014 AN: 79608 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00430

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000768

Gnomad OTH AF: 0.00973

GnomAD4 exome AF: 0.000778 AC: 740 AN: 951426 Hom.: 6 AF XY: 0.000635 AC XY: 312 AN XY: 491212

Gnomad4 AFR exome AF: 0.0287

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000406

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.0128 AC: 1019 AN: 79700 Hom.: 19 Cov.: 0 AF XY: 0.0124 AC XY: 466 AN XY: 37550

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.00429

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000435

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000768

Gnomad4 OTH AF: 0.00951

Alfa AF: 0.00725 Hom.: 0

Asia WGS AF: 0.00203 AC: 7 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2019

- -

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: rs375777357; hg19: chr4-88532181;