1-168728970-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001937.5(DPT):c.205T>A(p.Ser69Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,614,126 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (3 hom.)
• Consequence: DPT NM_001937.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.81

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-168728970-A-T is Benign according to our data. Variant chr1-168728970-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 710259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPT	NM_001937.5	c.205T>A	p.Ser69Thr	missense_variant	1/4	ENST00000367817.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPT	ENST00000367817.4	c.205T>A	p.Ser69Thr	missense_variant	1/4	1	NM_001937.5	P1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00162 AC: 408 AN: 251366 Hom.: 3 AF XY: 0.00161 AC XY: 219 AN XY: 135860

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00217

Gnomad NFE exome AF: 0.00292

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00255 AC: 3731 AN: 1461892 Hom.: 3 Cov.: 33 AF XY: 0.00244 AC XY: 1777 AN XY: 727248

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00200

Gnomad4 NFE exome AF: 0.00313

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74434

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000738 Hom.: 0

Bravo AF: 0.00118

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00195 AC: 237

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.30
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Benign	0.086	T
Sift4G	Uncertain	0.034	D
Polyphen		0.94	P
Vest4		0.64
MVP		0.88
MPC		0.18
ClinPred		0.057	T
GERP RS		5.0
Varity_R		0.21
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.25		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143980534; hg19: chr1-168698208;