Variant 3-58192792-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

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=0.18765235).

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 id is 2976230.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.905 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1L3	NM_004944.4 linkuse as main transcript	c.813C>T	p.Val271Val	synonymous_variant	8/8	ENST00000394549.7	NP_004935.1	Q13609-1A0A024R365
DNASE1L3	NM_001256560.2 linkuse as main transcript	c.723C>T	p.Val241Val	synonymous_variant	7/7		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.813C>T	p.Val271Val	synonymous_variant	8/8	1	NM_004944.4	ENSP00000378053.2	Q13609-1
DNASE1L3	ENST00000477209.5 linkuse as main transcript	c.338C>T	p.Ser113Leu	missense_variant	4/4	2		ENSP00000417976.1	H7C4R7
DNASE1L3	ENST00000486455.5 linkuse as main transcript	c.723C>T	p.Val241Val	synonymous_variant	7/7	2		ENSP00000419052.1	Q13609-2
DNASE1L3	ENST00000483681 linkuse as main transcript	c.*485C>T		3_prime_UTR_variant	9/9	5		ENSP00000417047.1	A0A0A0MT68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251056

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135688

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.34

CADD

Benign

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

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

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

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