4-87656267-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004407.4(DMP1):c.-21-205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,078 control chromosomes in the GnomAD database, including 29,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (29525 hom., cov: 33)
• Consequence: DMP1 NM_004407.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.87

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-87656267-T-C is Benign according to our data. Variant chr4-87656267-T-C is described in ClinVar as [Benign]. Clinvar id is 1234211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMP1	NM_004407.4	c.-21-205T>C		intron_variant		ENST00000339673.11
DMP1	NM_001079911.3	c.-21-205T>C		intron_variant
DMP1	XM_011531705.3	c.67-205T>C		intron_variant
DMP1	XM_011531706.3	c.67-205T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMP1	ENST00000339673.11	c.-21-205T>C		intron_variant		1	NM_004407.4	P1
	ENST00000506480.5	n.322+16723A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92201 AN: 151960 Hom.: 29484 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.558

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.607 AC: 92308 AN: 152078 Hom.: 29525 Cov.: 33 AF XY: 0.610 AC XY: 45351 AN XY: 74336

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.561

Alfa AF: 0.557 Hom.: 3147

Bravo AF: 0.612

Asia WGS AF: 0.684 AC: 2375 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.12
Dann	Benign	0.47

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: rs2627702; hg19: chr4-88577419;