3-58192753-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_004944.4(DNASE1L3):ā€‹c.852A>Gā€‹(p.Ser284Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,030 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

DNASE1L3
NM_004944.4 synonymous

Scores

14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534
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]

Genome browser will be placed here

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=0.090128005).
BP6
Variant 3-58192753-T-C is Benign according to our data. Variant chr3-58192753-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2868013.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.534 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNASE1L3NM_004944.4 linkuse as main transcriptc.852A>G p.Ser284Ser synonymous_variant 8/8 ENST00000394549.7 NP_004935.1 Q13609-1A0A024R365
DNASE1L3NM_001256560.2 linkuse as main transcriptc.762A>G p.Ser254Ser synonymous_variant 7/7 NP_001243489.1 Q13609-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNASE1L3ENST00000394549.7 linkuse as main transcriptc.852A>G p.Ser284Ser synonymous_variant 8/81 NM_004944.4 ENSP00000378053.2 Q13609-1
DNASE1L3ENST00000477209.5 linkuse as main transcriptc.377A>G p.Gln126Arg missense_variant 4/42 ENSP00000417976.1 H7C4R7
DNASE1L3ENST00000486455.5 linkuse as main transcriptc.762A>G p.Ser254Ser synonymous_variant 7/72 ENSP00000419052.1 Q13609-2
DNASE1L3ENST00000483681 linkuse as main transcriptc.*524A>G 3_prime_UTR_variant 9/95 ENSP00000417047.1 A0A0A0MT68

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251460
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461858
Hom.:
0
Cov.:
29
AF XY:
0.0000110
AC XY:
8
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000354
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
6.9
DANN
Benign
0.95
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.18
T
MetaRNN
Benign
0.090
T
MetaSVM
Benign
-0.91
T
PROVEAN
Benign
-0.78
N
REVEL
Benign
0.022
Sift
Benign
0.59
T
Sift4G
Benign
0.75
T
MutPred
0.28
Loss of glycosylation at P130 (P = 0.025);
MVP
0.48
ClinPred
0.034
T
GERP RS
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs759238109; hg19: chr3-58178480; API