16-3655478-G-C

Position:

chr16-3655478-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005223.4(DNASE1):c.105G>C(p.Glu35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,614,164 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 32 hom. )

Consequence

DNASE1
NM_005223.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.603

Variant links:

Genes affected

DNASE1 (HGNC:2956): (deoxyribonuclease 1) This gene encodes a member of the DNase family. This protein is stored in the zymogen granules of the nuclear envelope and functions by cleaving DNA in an endonucleolytic manner. At least six autosomal codominant alleles have been characterized, DNASE1*1 through DNASE1*6, and the sequence of DNASE1*2 represented in this record. Mutations in this gene have been associated with systemic lupus erythematosus (SLE), an autoimmune disease. A recombinant form of this protein is used to treat the one of the symptoms of cystic fibrosis by hydrolyzing the extracellular DNA in sputum and reducing its viscosity. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

DNASE1 links:

LOC124903631 (HGNC:):

LOC124903631 links:

TRAP1 (HGNC:16264): (TNF receptor associated protein 1) This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064407587).

BP6

Variant 16-3655478-G-C is Benign according to our data. Variant chr16-3655478-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646119.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-3655478-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1	NM_005223.4 link	c.105G>C	p.Glu35Asp	missense_variant	2/9	ENST00000246949.10	NP_005214.2	P24855-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNASE1	ENST00000246949.10 link	c.105G>C	p.Glu35Asp	missense_variant	2/9	1	NM_005223.4	ENSP00000246949.5		P24855-1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

541

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00384

AC:

966

AN:

251406

Hom.:

AF XY:

0.00396

AC XY:

538

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00702

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00478

AC:

6993

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

3477

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00302

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000684

Gnomad4 FIN exome

AF:

0.00660

Gnomad4 NFE exome

AF:

0.00544

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00355

AC:

541

AN:

152332

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

287

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.00541

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00498

Hom.:

Bravo

AF:

0.00348

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00396

AC:

481

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00652

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

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

DNASE1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0064

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.020

Sift

Benign

0.72

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.16

MutPred

0.37

Loss of ubiquitination at K37 (P = 0.073);Loss of ubiquitination at K37 (P = 0.073);

MVP

0.42

MPC

0.0067

ClinPred

0.0027

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.62

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.

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