Variant 1-168696554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001937.5(DPT):c.601G>A(p.Val201Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,934 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0063 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 19 hom. )

Consequence

DPT
NM_001937.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043096244).

BP6

Variant 1-168696554-C-T is Benign according to our data. Variant chr1-168696554-C-T is described in ClinVar as [Benign]. Clinvar id is 728993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00634 (966/152300) while in subpopulation AFR AF= 0.0221 (918/41550). AF 95% confidence interval is 0.0209. There are 8 homozygotes in gnomad4. There are 456 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPT	NM_001937.5 linkuse as main transcript	c.601G>A	p.Val201Ile	missense_variant	4/4	ENST00000367817.4	NP_001928.2	Q07507

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPT	ENST00000367817.4 linkuse as main transcript	c.601G>A	p.Val201Ile	missense_variant	4/4	1	NM_001937.5	ENSP00000356791.3		Q07507
ENSG00000285622	ENST00000650631.1 linkuse as main transcript	n.1001G>A		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

959

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00172

AC:

432

AN:

251094

Hom.:

AF XY:

0.00116

AC XY:

157

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000804

AC:

1175

AN:

1461634

Hom.:

Cov.:

AF XY:

0.000729

AC XY:

530

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00634

AC:

966

AN:

152300

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

456

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00734

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00198

AC:

240

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.16

REVEL

Benign

0.037

Sift

Benign

0.055

Sift4G

Benign

0.16

Polyphen

0.21

Vest4

0.18

MVP

0.67

MPC

0.40

ClinPred

0.016

GERP RS

5.6

Varity_R

0.069

gMVP

0.31

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