Variant 17-43774881-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004090.4(DUSP3):c.183C>T(p.Asn61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,614,198 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

DUSP3
NM_004090.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.421

Variant links:

Genes affected

DUSP3 (HGNC:3069): (dual specificity phosphatase 3) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1. [provided by RefSeq, Jul 2008]

DUSP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-43774881-G-A is Benign according to our data. Variant chr17-43774881-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647815.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.421 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP3	NM_004090.4 linkuse as main transcript	c.183C>T	p.Asn61=	synonymous_variant	2/3	ENST00000226004.8	NP_004081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP3	ENST00000226004.8 linkuse as main transcript	c.183C>T	p.Asn61=	synonymous_variant	2/3	1	NM_004090.4	ENSP00000226004	P1	P51452-1
DUSP3	ENST00000590342.1 linkuse as main transcript	c.*330C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	1		ENSP00000467424
DUSP3	ENST00000590935.1 linkuse as main transcript	c.60C>T	p.Asn20=	synonymous_variant	1/3	5		ENSP00000468604
DUSP3	ENST00000591618.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00382

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00191

AC:

481

AN:

251378

Hom.:

AF XY:

0.00197

AC XY:

267

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00220

AC:

3210

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1624

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000591

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00260

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00209

AC:

318

AN:

152308

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00382

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00207

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, 2022

DUSP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.4

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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