Genetic Variant DUSP1:p.Thr363Ala (chr5-172768779-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004417.4(DUSP1):c.1087A>G(p.Thr363Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,517,788 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DUSP1
NM_004417.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

Publications

0 publications found

Variant links:

Genes affected

DUSP1 (HGNC:3064): (dual specificity phosphatase 1) The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]

DUSP1 links:

ENSG00000253736 (HGNC:):

ENSG00000253736 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1844151).

BS2

High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004417.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	NM_004417.4	MANE Select	c.1087A>G	p.Thr363Ala	missense	Exon 4 of 4	NP_004408.1	P28562

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP1	ENST00000239223.4	TSL:1 MANE Select	c.1087A>G	p.Thr363Ala	missense	Exon 4 of 4	ENSP00000239223.3	P28562
DUSP1	ENST00000868089.1		c.1087A>G	p.Thr363Ala	missense	Exon 4 of 5	ENSP00000538148.1
DUSP1	ENST00000868090.1		c.1087A>G	p.Thr363Ala	missense	Exon 4 of 5	ENSP00000538149.1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

183124

AF XY:

0.0000311

show subpopulations

Gnomad AFR exome

AF:

0.000392

Gnomad AMR exome

AF:

0.0000441

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1365808

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

668764

show subpopulations

African (AFR)

AF:

0.000427

AC:

AN:

30446

American (AMR)

AF:

0.00

AC:

AN:

31036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20174

East Asian (EAS)

AF:

0.00

AC:

AN:

38152

South Asian (SAS)

AF:

0.00

AC:

AN:

71338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063184

Other (OTH)

AF:

0.0000534

AC:

AN:

56158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.000118

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.000435

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000419

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.022

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.4

PhyloP100

5.9

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.4

REVEL

Benign

0.24

Sift

Benign

0.24

Sift4G

Benign

0.34

Polyphen

1.0

Vest4

0.39

MVP

0.80

MPC

0.72

ClinPred

0.088

GERP RS

5.6

Varity_R

0.14

gMVP

0.66

Mutation Taster

=44/56

disease causing

(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