3-58192798-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 3645801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.323 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L3	NM_004944.4	c.807G>C	p.Leu269Leu	synonymous_variant	Exon 8 of 8	ENST00000394549.7	NP_004935.1
DNASE1L3	NM_001256560.2	c.717G>C	p.Leu239Leu	synonymous_variant	Exon 7 of 7		NP_001243489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L3	ENST00000394549.7	c.807G>C	p.Leu269Leu	synonymous_variant	Exon 8 of 8	1	NM_004944.4	ENSP00000378053.2
DNASE1L3	ENST00000477209.5	c.332G>C	p.Trp111Ser	missense_variant	Exon 4 of 4	2		ENSP00000417976.1
DNASE1L3	ENST00000486455.5	c.717G>C	p.Leu239Leu	synonymous_variant	Exon 7 of 7	2		ENSP00000419052.1
DNASE1L3	ENST00000483681	c.*479G>C		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000417047.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 20, 2024

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
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-58178525;