rs2615498

Positions:

chr4-87662996-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004407.4(DMP1):c.1218C>T(p.Ser406=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,888 control chromosomes in the GnomAD database, including 33,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2259 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30786 hom. )

Consequence

DMP1
NM_004407.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 4-87662996-C-T is Benign according to our data. Variant chr4-87662996-C-T is described in ClinVar as [Benign]. Clinvar id is 349982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-87662996-C-T is described in Lovd as [Benign]. Variant chr4-87662996-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMP1	NM_004407.4 linkuse as main transcript	c.1218C>T	p.Ser406=	synonymous_variant	6/6	ENST00000339673.11	NP_004398.1
LOC105377323	XR_938960.3 linkuse as main transcript	n.649-5587G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMP1	ENST00000339673.11 linkuse as main transcript	c.1218C>T	p.Ser406=	synonymous_variant	6/6	1	NM_004407.4	ENSP00000340935	P1	Q13316-1
	ENST00000506480.5 linkuse as main transcript	n.322+9994G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24171

AN:

151990

Hom.:

2258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.189

AC:

47402

AN:

251038

Hom.:

4927

AF XY:

0.198

AC XY:

26858

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.202

AC:

294738

AN:

1461780

Hom.:

30786

Cov.:

AF XY:

0.205

AC XY:

148863

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0585

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.159

AC:

24183

AN:

152108

Hom.:

2259

Cov.:

AF XY:

0.161

AC XY:

11954

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0653

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.177

Hom.:

1383

Bravo

AF:

0.148

Asia WGS

AF:

0.278

AC:

965

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.197

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hypophosphatemic rickets, autosomal recessive, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.27

DANN

Benign

0.54

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