rs61731008

Positions:

• chr4-87612489-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014208.3(DSPP):​c.303C>T​(p.Asn101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,532 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (4 hom.)
• Consequence: DSPP NM_014208.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.37

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-87612489-C-T is Benign according to our data. Variant chr4-87612489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-87612489-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BS2: High AC in GnomAd4 at 596 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSPP	NM_014208.3	c.303C>T	p.Asn101=	synonymous_variant	4/5	ENST00000651931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSPP	ENST00000651931.1	c.303C>T	p.Asn101=	synonymous_variant	4/5		NM_014208.3	P1
	ENST00000506480.5	n.323-43956G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 594 AN: 151692 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00115 AC: 287 AN: 249008 Hom.: 1 AF XY: 0.000896 AC XY: 121 AN XY: 135086

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000704 AC: 1029 AN: 1461722 Hom.: 4 Cov.: 84 AF XY: 0.000668 AC XY: 486 AN XY: 727142

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000419

Gnomad4 OTH exome AF: 0.000662

GnomAD4 genome AF: 0.00393 AC: 596 AN: 151810 Hom.: 4 Cov.: 32 AF XY: 0.00392 AC XY: 291 AN XY: 74190

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000626

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00156 Hom.: 0

Bravo AF: 0.00402

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 21, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.56

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: rs61731008; hg19: chr4-88533641; COSMIC: COSV99217058;