Genetic Variant NM_004944.4:c.813C>T (chr3-58192792-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_004944.4(DNASE1L3):c.813C>T(p.Val271Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DNASE1L3
NM_004944.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.905

Publications

0 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18765235).

BP6

Variant 3-58192792-G-A is Benign according to our data. Variant chr3-58192792-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2976230.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.905 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004944.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	NM_004944.4	MANE Select	c.813C>T	p.Val271Val	synonymous	Exon 8 of 8	NP_004935.1	Q13609-1
	DNASE1L3	NM_001256560.2		c.723C>T	p.Val241Val	synonymous	Exon 7 of 7	NP_001243489.1	Q13609-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNASE1L3	ENST00000394549.7	TSL:1 MANE Select	c.813C>T	p.Val271Val	synonymous	Exon 8 of 8	ENSP00000378053.2	Q13609-1
DNASE1L3	ENST00000477209.5	TSL:2	c.338C>T	p.Ser113Leu	missense	Exon 4 of 4	ENSP00000417976.1	H7C4R7
DNASE1L3	ENST00000907344.1		c.840C>T	p.Val280Val	synonymous	Exon 8 of 8	ENSP00000577403.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251056

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111928

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.048

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.35

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

PhyloP100

0.91

PROVEAN

Benign

-1.6

REVEL

Benign

0.060

Sift

Benign

0.089

Sift4G

Benign

0.074

MutPred

0.50

Loss of glycosylation at T115 (P = 0.0442)

MVP

0.38

ClinPred

0.12

GERP RS

4.0

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over