rs35677470

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes

AF:

0.0483

AC:

12137

AN:

251140

Hom.:

411

AF XY:

0.0497

AC XY:

6747

AN XY:

135708

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 SAS exome

AF:

0.0362

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

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.0225

Gnomad4 ASJ exome

AF:

0.0269

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0355

Gnomad4 FIN exome

AF:

0.0575

Gnomad4 NFE exome

AF:

0.0790

Gnomad4 OTH exome

AF:

0.0570

GnomAD4 genome

AF:

0.0461

AC:

7017

AN:

152300

Hom.:

213

Cov.:

AF XY:

0.0448

AC XY:

3334

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0278

Gnomad4 FIN

AF:

0.0574

Gnomad4 NFE

AF:

0.0757

Gnomad4 OTH

AF:

0.0354

Alfa

AF:

0.0672

Hom.:

649

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

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

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

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