NM_004944.4:c.807G>C

Variant names:

• chr3-58192798-C-G
• NM_004944.4:c.807G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_004944.4(DNASE1L3):​c.807G>C​(p.Leu269Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: DNASE1L3 NM_004944.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.323
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33463332).
• BP6: Variant 3-58192798-C-G is Benign according to our data. Variant chr3-58192798-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3645801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.323 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.807G>C	p.Leu269Leu	synonymous	Exon 8 of 8	NP_004935.1	Q13609-1
	DNASE1L3	NM_001256560.2		c.717G>C	p.Leu239Leu	synonymous	Exon 7 of 7	NP_001243489.1	Q13609-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L3	ENST00000394549.7	TSL:1 MANE Select	c.807G>C	p.Leu269Leu	synonymous	Exon 8 of 8	ENSP00000378053.2	Q13609-1
	DNASE1L3	ENST00000477209.5	TSL:2	c.332G>C	p.Trp111Ser	missense	Exon 4 of 4	ENSP00000417976.1	H7C4R7
	DNASE1L3	ENST00000907344.1		c.834G>C	p.Leu278Leu	synonymous	Exon 8 of 8	ENSP00000577403.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	6.6
DANN	Benign	0.97
Eigen	Benign	0.033
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.080	D
PhyloP100		-0.32
PROVEAN	Benign	0.77	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.034	D
MutPred		0.74		Gain of disorder (P = 0.0014)
MVP		0.74
ClinPred		0.13	T
GERP RS		3.9
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr3-58178525;