Variant 4-87615883-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_014208.3(DSPP):c.3221A>T(p.Asp1074Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 120,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1074AAATAVIAVTAV?) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000083 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0024 ( 485 hom. )

Failed GnomAD Quality Control

Consequence

DSPP
NM_014208.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.32

Variant links:

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]

DSPP links:

ENSG00000249001 (HGNC:):

ENSG00000249001 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DSPP. . Trascript score misZ 3.203 (greater than threshold 3.09). GenCC has associacion of gene with dentin dysplasia type I, dentinogenesis imperfecta, deafness, autosomal dominant 39, with dentinogenesis imperfecta 1, dentin dysplasia type II, dentinogenesis imperfecta type 2, dentinogenesis imperfecta type 3.

BP4

Computational evidence support a benign effect (MetaRNN=0.33864444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSPP	NM_014208.3 linkuse as main transcript	c.3221A>T	p.Asp1074Val	missense_variant	5/5	ENST00000651931.1	NP_055023.2	Q9NZW4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSPP	ENST00000651931.1 linkuse as main transcript	c.3221A>T	p.Asp1074Val	missense_variant	5/5		NM_014208.3	ENSP00000498766.1		Q9NZW4
ENSG00000249001	ENST00000506480.5 linkuse as main transcript	n.323-47350T>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000833

AC:

AN:

120060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00238

AC:

1832

AN:

769970

Hom.:

485

Cov.:

155

AF XY:

0.00253

AC XY:

967

AN XY:

382338

show subpopulations

Gnomad4 AFR exome

AF:

0.000337

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00217

Gnomad4 EAS exome

AF:

0.00582

Gnomad4 SAS exome

AF:

0.000190

Gnomad4 FIN exome

AF:

0.00403

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.00000833

AC:

AN:

120060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000129

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.10

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.0

PROVEAN

Benign

-2.0

REVEL

Benign

0.26

Sift4G

Benign

0.22

Polyphen

0.99

Vest4

0.41

MutPred

0.25

Gain of glycosylation at S1070 (P = 4e-04);

MVP

0.87

ClinPred

0.16

GERP RS

1.5

Varity_R

0.38

gMVP

0.0013

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over