Variant chr3-58193301-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004944.4(DNASE1L3):c.801+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,603,380 control chromosomes in the GnomAD database, including 96,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8368 hom., cov: 30)

Exomes 𝑓: 0.34 ( 88454 hom. )

Consequence

DNASE1L3
NM_004944.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.635

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-58193301-T-C is Benign according to our data. Variant chr3-58193301-T-C is described in ClinVar as [Benign]. Clinvar id is 2688407.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-58193301-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1L3	NM_004944.4 linkuse as main transcript	c.801+42A>G		intron_variant		ENST00000394549.7	NP_004935.1	Q13609-1A0A024R365
DNASE1L3	NM_001256560.2 linkuse as main transcript	c.711+42A>G		intron_variant			NP_001243489.1	Q13609-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNASE1L3	ENST00000394549.7 linkuse as main transcript	c.801+42A>G		intron_variant		1	NM_004944.4	ENSP00000378053.2	Q13609-1
DNASE1L3	ENST00000483681.5 linkuse as main transcript	c.843A>G	p.Lys281Lys	synonymous_variant	9/9	5		ENSP00000417047.1	A0A0A0MT68
DNASE1L3	ENST00000486455.5 linkuse as main transcript	c.711+42A>G		intron_variant		2		ENSP00000419052.1	Q13609-2
DNASE1L3	ENST00000477209.5 linkuse as main transcript	c.327-498A>G		intron_variant		2		ENSP00000417976.1	H7C4R7

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48257

AN:

151818

Hom.:

8372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.287

GnomAD3 exomes

AF:

0.366

AC:

91426

AN:

250000

Hom.:

18085

AF XY:

0.367

AC XY:

49625

AN XY:

135140

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.645

Gnomad SAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.342

AC:

496325

AN:

1451446

Hom.:

88454

Cov.:

AF XY:

0.344

AC XY:

248376

AN XY:

722674

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.613

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.318

AC:

48274

AN:

151934

Hom.:

8368

Cov.:

AF XY:

0.325

AC XY:

24139

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.350

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.291

Alfa

AF:

0.317

Hom.:

15452

Bravo

AF:

0.313

Asia WGS

AF:

0.549

AC:

1908

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.76

DANN

Benign

0.52

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