rs762157486
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4BP6BS2
The NM_014208.3(DSPP):c.3033_3041del(p.Asp1014_Ser1016del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,520,544 control chromosomes in the GnomAD database, including 40 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0061 ( 37 hom. )
Consequence
DSPP
NM_014208.3 inframe_deletion
NM_014208.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.20
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_014208.3.
BP6
?
Variant 4-87615677-TAGCAGTGAC-T is Benign according to our data. Variant chr4-87615677-TAGCAGTGAC-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445476.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
?
High AC in GnomAd4 at 521 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSPP | NM_014208.3 | c.3033_3041del | p.Asp1014_Ser1016del | inframe_deletion | 5/5 | ENST00000651931.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSPP | ENST00000651931.1 | c.3033_3041del | p.Asp1014_Ser1016del | inframe_deletion | 5/5 | NM_014208.3 | P1 | ||
ENST00000506480.5 | n.323-47153_323-47145del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00372 AC: 520AN: 139900Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00359 AC: 545AN: 151648Hom.: 5 AF XY: 0.00382 AC XY: 307AN XY: 80418
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GnomAD4 exome AF: 0.00606 AC: 8368AN: 1380534Hom.: 37 AF XY: 0.00610 AC XY: 4152AN XY: 680344
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GnomAD4 genome ? AF: 0.00372 AC: 521AN: 140010Hom.: 3 Cov.: 33 AF XY: 0.00351 AC XY: 240AN XY: 68422
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | DSPP: BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 22, 2017 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at