Variant 4-87657079-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004407.4(DMP1):c.102G>T(p.Lys34Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000138 in 1,372,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DMP1
NM_004407.4 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

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:

DMP1 (HGNC:):

DMP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMP1	NM_004407.4 linkuse as main transcript	c.102G>T	p.Lys34Asn	missense_variant, splice_region_variant	3/6	ENST00000339673.11	NP_004398.1	Q13316-1
DMP1	NM_001079911.3 linkuse as main transcript	c.102G>T	p.Lys34Asn	missense_variant, splice_region_variant	3/5		NP_001073380.1	Q13316-2
DMP1	XM_011531705.3 linkuse as main transcript	c.189G>T	p.Lys63Asn	missense_variant, splice_region_variant	3/6		XP_011530007.1
DMP1	XM_011531706.3 linkuse as main transcript	c.189G>T	p.Lys63Asn	missense_variant, splice_region_variant	3/5		XP_011530008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMP1	ENST00000339673.11 linkuse as main transcript	c.102G>T	p.Lys34Asn	missense_variant, splice_region_variant	3/6	1	NM_004407.4	ENSP00000340935.6		Q13316-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249268

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1372838

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

687630

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypophosphatemic rickets, autosomal recessive, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.98

D;D

Vest4

0.28

MutPred

0.41

Loss of methylation at K34 (P = 0.002);Loss of methylation at K34 (P = 0.002);

MVP

0.92

MPC

0.37

ClinPred

0.89

GERP RS

5.8

Varity_R

0.19

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.96

SpliceAI score (max)

0.020

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