rs1052591

Positions:

• chr1-168728935-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001937.5(DPT):​c.240G>A​(p.Thr80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,916 control chromosomes in the GnomAD database, including 204,390 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15462 hom., cov: 32)
  • Exomes 𝑓: 0.50 (188928 hom.)
• Consequence: DPT NM_001937.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.42

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-5.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPT	NM_001937.5	c.240G>A	p.Thr80=	synonymous_variant	1/4	ENST00000367817.4	NP_001928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPT	ENST00000367817.4	c.240G>A	p.Thr80=	synonymous_variant	1/4	1	NM_001937.5	ENSP00000356791	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65993 AN: 151920 Hom.: 15465 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.444

GnomAD3 exomes AF: 0.427 AC: 107125 AN: 250962 Hom.: 25119 AF XY: 0.435 AC XY: 58999 AN XY: 135698

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.462

GnomAD4 exome AF: 0.499 AC: 730028 AN: 1461878 Hom.: 188928 Cov.: 73 AF XY: 0.497 AC XY: 361119 AN XY: 727240

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.434 AC: 65997 AN: 152038 Hom.: 15462 Cov.: 32 AF XY: 0.426 AC XY: 31637 AN XY: 74342

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.443

Alfa AF: 0.504 Hom.: 37813

Bravo AF: 0.417

Asia WGS AF: 0.265 AC: 922 AN: 3478

EpiCase AF: 0.526

EpiControl AF: 0.519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.11
DANN	Benign	0.81

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: rs1052591; hg19: chr1-168698173; COSMIC: COSV63189989;