Genetic Variant DPT:p.Arg138Arg (chr1-168714238-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001937.5(DPT):c.414G>A(p.Arg138Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,614,010 control chromosomes in the GnomAD database, including 2,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.041 ( 165 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2778 hom. )

Consequence

DPT
NM_001937.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.230

Variant links:

Genes affected

DPT (HGNC:3011): (dermatopontin) Dermatopontin is an extracellular matrix protein with possible functions in cell-matrix interactions and matrix assembly. The protein is found in various tissues and many of its tyrosine residues are sulphated. Dermatopontin is postulated to modify the behavior of TGF-beta through interaction with decorin. [provided by RefSeq, Jul 2008]

DPT links:

ENSG00000285622 (HGNC:):

ENSG00000285622 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-168714238-C-T is Benign according to our data. Variant chr1-168714238-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3273675.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPT	NM_001937.5 link	c.414G>A	p.Arg138Arg	synonymous_variant	Exon 2 of 4	ENST00000367817.4	NP_001928.2	Q07507

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPT	ENST00000367817.4 link	c.414G>A	p.Arg138Arg	synonymous_variant	Exon 2 of 4	1	NM_001937.5	ENSP00000356791.3		Q07507
ENSG00000285622	ENST00000650631.1 link	n.814G>A		non_coding_transcript_exon_variant	Exon 7 of 9

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6219

AN:

152072

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0690

Gnomad FIN

AF:

0.0354

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0627

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0476

AC:

11963

AN:

251260

Hom.:

381

AF XY:

0.0507

AC XY:

6883

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0731

Gnomad FIN exome

AF:

0.0384

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0483

GnomAD4 exome

AF:

0.0586

AC:

85664

AN:

1461820

Hom.:

2778

Cov.:

AF XY:

0.0592

AC XY:

43025

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00836

Gnomad4 AMR exome

AF:

0.0219

Gnomad4 ASJ exome

AF:

0.0377

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0730

Gnomad4 FIN exome

AF:

0.0397

Gnomad4 NFE exome

AF:

0.0642

Gnomad4 OTH exome

AF:

0.0543

GnomAD4 genome

AF:

0.0409

AC:

6217

AN:

152190

Hom.:

165

Cov.:

AF XY:

0.0400

AC XY:

2974

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0338

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0687

Gnomad4 FIN

AF:

0.0354

Gnomad4 NFE

AF:

0.0627

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0299

Hom.:

Bravo

AF:

0.0385

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0631

EpiControl

AF:

0.0609

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.4

DANN

Benign

0.87

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