rs35677470

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004944.4(DNASE1L3):c.616C>T(p.Arg206Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0661 in 1,614,064 control chromosomes in the GnomAD database, including 4,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.046 ( 213 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3797 hom. )

Consequence

DNASE1L3
NM_004944.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.53

Publications

65 publications found

Variant links:

Genes affected

DNASE1L3 (HGNC:2959): (deoxyribonuclease 1 like 3) This gene encodes a member of the deoxyribonuclease I family. The encoded protein hydrolyzes DNA, is not inhibited by actin, and mediates the breakdown of DNA during apoptosis. Mutations in this gene are a cause of systemic lupus erythematosus-16. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

DNASE1L3 Gene-Disease associations (from GenCC):

autosomal systemic lupus erythematosus type 16
Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
hypocomplementemic urticarial vasculitis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNASE1L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02154231).

BP6

Variant 3-58197909-G-A is Benign according to our data. Variant chr3-58197909-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1146799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L3	NM_004944.4 link	c.616C>T	p.Arg206Cys	missense_variant	Exon 6 of 8	ENST00000394549.7	NP_004935.1	Q13609-1A0A024R365
DNASE1L3	NM_001256560.2 link	c.526C>T	p.Arg176Cys	missense_variant	Exon 5 of 7		NP_001243489.1	Q13609-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNASE1L3	ENST00000394549.7 link	c.616C>T	p.Arg206Cys	missense_variant	Exon 6 of 8	1	NM_004944.4	ENSP00000378053.2	Q13609-1
DNASE1L3	ENST00000483681.5 link	c.616C>T	p.Arg206Cys	missense_variant	Exon 8 of 9	5		ENSP00000417047.1	A0A0A0MT68
DNASE1L3	ENST00000486455.5 link	c.526C>T	p.Arg176Cys	missense_variant	Exon 5 of 7	2		ENSP00000419052.1	Q13609-2
DNASE1L3	ENST00000477209.5 link	c.238C>T	p.Arg80Cys	missense_variant	Exon 3 of 4	2		ENSP00000417976.1	H7C4R7

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7016

AN:

152182

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0276

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0358

GnomAD2 exomes

AF:

0.0483

AC:

12137

AN:

251140

AF XY:

0.0497

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0730

Gnomad OTH exome

AF:

0.0529

GnomAD4 exome

AF:

0.0681

AC:

99615

AN:

1461764

Hom.:

3797

Cov.:

AF XY:

0.0674

AC XY:

48981

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.0106

AC:

355

AN:

33476

American (AMR)

AF:

0.0225

AC:

1006

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

702

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0355

AC:

3064

AN:

86232

European-Finnish (FIN)

AF:

0.0575

AC:

3072

AN:

53420

Middle Eastern (MID)

AF:

0.0276

AC:

159

AN:

5756

European-Non Finnish (NFE)

AF:

0.0790

AC:

87813

AN:

1111950

Other (OTH)

AF:

0.0570

AC:

3441

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5067

10134

15200

20267

25334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3190

6380

9570

12760

15950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0461

AC:

7017

AN:

152300

Hom.:

213

Cov.:

AF XY:

0.0448

AC XY:

3334

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0134

AC:

556

AN:

41566

American (AMR)

AF:

0.0235

AC:

360

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0278

AC:

134

AN:

4822

European-Finnish (FIN)

AF:

0.0574

AC:

609

AN:

10618

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0757

AC:

5145

AN:

68004

Other (OTH)

AF:

0.0354

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

339

679

1018

1358

1697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0643

Hom.:

1395

Bravo

AF:

0.0427

TwinsUK

AF:

0.0906

AC:

336

ALSPAC

AF:

0.0763

AC:

294

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0751

AC:

646

ExAC

AF:

0.0484

AC:

5876

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0678

EpiControl

AF:

0.0710

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.71

.;.;.;D

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.7

.;.;.;H

PhyloP100

4.5

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.7

D;D;D;D

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;.;.;D

Vest4

0.63

ClinPred

0.12

GERP RS

5.3

Varity_R

0.89

gMVP

0.88

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over