Genetic Variant DUSP3:n.*1214G>A (chr17-43769100-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000590342.1(DUSP3):n.*1214G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 153,440 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2217 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27 hom. )

Consequence

DUSP3
ENST00000590342.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.326

Publications

16 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590342.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP3	NM_004090.4	MANE Select	c.*509G>A		3_prime_UTR	Exon 3 of 3	NP_004081.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DUSP3	ENST00000590342.1	TSL:1	n.*1214G>A	non_coding_transcript_exon	Exon 4 of 4	ENSP00000467424.1
DUSP3	ENST00000226004.8	TSL:1 MANE Select	c.*509G>A	3_prime_UTR	Exon 3 of 3	ENSP00000226004.2
DUSP3	ENST00000590342.1	TSL:1	n.*1214G>A	3_prime_UTR	Exon 4 of 4	ENSP00000467424.1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23082

AN:

152132

Hom.:

2217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.195

AC:

232

AN:

1190

Hom.:

Cov.:

AF XY:

0.191

AC XY:

130

AN XY:

680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.200

AC:

AN:

European-Finnish (FIN)

AF:

0.258

AC:

116

AN:

450

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.157

AC:

AN:

612

Other (OTH)

AF:

0.152

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23084

AN:

152250

Hom.:

2217

Cov.:

AF XY:

0.152

AC XY:

11305

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0493

AC:

2050

AN:

41558

American (AMR)

AF:

0.135

AC:

2066

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1032

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.174

AC:

839

AN:

4824

European-Finnish (FIN)

AF:

0.213

AC:

2252

AN:

10596

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14263

AN:

68006

Other (OTH)

AF:

0.170

AC:

359

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

983

1966

2949

3932

4915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.183

Hom.:

1542

Bravo

AF:

0.141

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.2

(source)

DANN

Benign

0.52

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over