Genetic Variant DUSP1:p.Thr363Ser (chr5-172768779-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004417.4(DUSP1):c.1087A>T(p.Thr363Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000732 in 1,365,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T363A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

DUSP1
NM_004417.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.370534).

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>T	p.Thr363Ser	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>T	p.Thr363Ser	missense	Exon 4 of 4	ENSP00000239223.3	P28562
DUSP1	ENST00000868089.1		c.1087A>T	p.Thr363Ser	missense	Exon 4 of 5	ENSP00000538148.1
DUSP1	ENST00000868090.1		c.1087A>T	p.Thr363Ser	missense	Exon 4 of 5	ENSP00000538149.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1365808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668764

show subpopulations

African (AFR)

AF:

0.00

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:

9.41e-7

AC:

AN:

1063184

Other (OTH)

AF:

0.00

AC:

AN:

56158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.011

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

PhyloP100

5.9

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.026

Polyphen

1.0

Vest4

0.27

MutPred

0.11

Loss of glycosylation at T363 (P = 0.0504)

MVP

0.83

MPC

0.99

ClinPred

0.92

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.46

Mutation Taster

=60/40

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over