Variant chr16-3656667-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005223.4(DNASE1):c.350A>C(p.Tyr117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,612,976 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 15 hom., cov: 31)

Exomes 𝑓: 0.012 ( 173 hom. )

Consequence

DNASE1
NM_005223.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.55

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=0.008581221).

BP6

Variant 16-3656667-A-C is Benign according to our data. Variant chr16-3656667-A-C is described in ClinVar as [Benign]. Clinvar id is 2672612.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNASE1	NM_005223.4 link	c.350A>C	p.Tyr117Ser	missense_variant	5/9	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.350A>C	p.Tyr117Ser	missense_variant	5/9	1	NM_005223.4	ENSP00000246949.5		P24855-1

Frequencies

GnomAD3 genomes

AF:

0.00979

AC:

1489

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.0105

AC:

2615

AN:

249202

Hom.:

AF XY:

0.00985

AC XY:

1328

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00546

Gnomad ASJ exome

AF:

0.00956

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00218

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0123

AC:

17956

AN:

1460766

Hom.:

173

Cov.:

AF XY:

0.0117

AC XY:

8507

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00605

Gnomad4 ASJ exome

AF:

0.00762

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00977

AC:

1487

AN:

152210

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

800

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00824

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00228

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.0105

AC:

1280

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

DNASE1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

D;D

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-8.4

D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.18

MPC

0.030

ClinPred

0.093

GERP RS

4.4

Varity_R

0.95

gMVP

0.80

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