Variant 4-87656602-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004407.4(DMP1):c.54+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,177,600 control chromosomes in the GnomAD database, including 24,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2698 hom., cov: 32)

Exomes 𝑓: 0.20 ( 21873 hom. )

Consequence

DMP1
NM_004407.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.261

Variant links:

Genes affected

DMP1 (HGNC:2932): (dentin matrix acidic phosphoprotein 1) Dentin matrix acidic phosphoprotein is an extracellular matrix protein and a member of the small integrin binding ligand N-linked glycoprotein family. This protein, which is critical for proper mineralization of bone and dentin, is present in diverse cells of bone and tooth tissues. The protein contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. In undifferentiated osteoblasts it is primarily a nuclear protein that regulates the expression of osteoblast-specific genes. During osteoblast maturation the protein becomes phosphorylated and is exported to the extracellular matrix, where it orchestrates mineralized matrix formation. Mutations in the gene are known to cause autosomal recessive hypophosphatemia, a disease that manifests as rickets and osteomalacia. The gene structure is conserved in mammals. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DMP1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-87656602-A-G is Benign according to our data. Variant chr4-87656602-A-G is described in ClinVar as [Benign]. Clinvar id is 1178697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DMP1	NM_004407.4 linkuse as main transcript	c.54+56A>G	intron_variant	ENST00000339673.11
DMP1	NM_001079911.3 linkuse as main transcript	c.54+56A>G	intron_variant
DMP1	XM_011531705.3 linkuse as main transcript	c.141+56A>G	intron_variant
DMP1	XM_011531706.3 linkuse as main transcript	c.141+56A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMP1	ENST00000339673.11 linkuse as main transcript	c.54+56A>G		intron_variant		1	NM_004407.4	P1	Q13316-1
	ENST00000506480.5 linkuse as main transcript	n.322+16388T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26379

AN:

152036

Hom.:

2700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0750

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.199

AC:

204303

AN:

1025446

Hom.:

21873

AF XY:

0.197

AC XY:

104401

AN XY:

529836

show subpopulations

Gnomad4 AFR exome

AF:

0.0722

Gnomad4 AMR exome

AF:

0.302

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.173

AC:

26385

AN:

152154

Hom.:

2698

Cov.:

AF XY:

0.172

AC XY:

12780

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0750

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.193

Hom.:

380

Bravo

AF:

0.178

Asia WGS

AF:

0.147

AC:

516

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.045

DANN

Benign

0.53

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over