chr3-58192726-A-G

Variant names:

• chr3-58192726-A-G
• NM_004944.4:c.879T>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_004944.4(DNASE1L3):​c.879T>C​(p.Ser293Ser) 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: 32)
• Consequence: DNASE1L3 NM_004944.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.394

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1200403).
• BP6: Variant 3-58192726-A-G is Benign according to our data. Variant chr3-58192726-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3651715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.394 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L3	NM_004944.4	c.879T>C	p.Ser293Ser	synonymous_variant	Exon 8 of 8	ENST00000394549.7	NP_004935.1
DNASE1L3	NM_001256560.2	c.789T>C	p.Ser263Ser	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.879T>C	p.Ser293Ser	synonymous_variant	Exon 8 of 8	1	NM_004944.4	ENSP00000378053.2
DNASE1L3	ENST00000477209.5	c.404T>C	p.Leu135Pro	missense_variant	Exon 4 of 4	2		ENSP00000417976.1
DNASE1L3	ENST00000486455.5	c.789T>C	p.Ser263Ser	synonymous_variant	Exon 7 of 7	2		ENSP00000419052.1
DNASE1L3	ENST00000483681	c.*551T>C		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000417047.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 30, 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	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	1.0
DANN	Benign	0.56
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
MutPred		0.44		Gain of relative solvent accessibility (P = 0.005);
MVP		0.22
ClinPred		0.062	T
GERP RS		-2.6

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: chr3-58178453;