Genetic Variant DUSP5:p.Ala59Pro (chr10-110498296-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004419.4(DUSP5):c.175G>C(p.Ala59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,284,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

DUSP5
NM_004419.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Publications

0 publications found

Variant links:

Genes affected

DUSP5 (HGNC:3071): (dual specificity phosphatase 5) 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 product inactivates ERK1, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

DUSP5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23094437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004419.4. 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
	DUSP5	NM_004419.4	MANE Select	c.175G>C	p.Ala59Pro	missense	Exon 1 of 4	NP_004410.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP5	ENST00000369583.4	TSL:1 MANE Select	c.175G>C	p.Ala59Pro	missense	Exon 1 of 4	ENSP00000358596.3	Q16690
DUSP5	ENST00000925260.1		c.175G>C	p.Ala59Pro	missense	Exon 1 of 4	ENSP00000595319.1
DUSP5	ENST00000895745.1		c.175G>C	p.Ala59Pro	missense	Exon 1 of 2	ENSP00000565804.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

159550

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000156

AC:

AN:

1284800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

637398

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27156

American (AMR)

AF:

0.00

AC:

AN:

32022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21098

East Asian (EAS)

AF:

0.00

AC:

AN:

29326

South Asian (SAS)

AF:

0.00

AC:

AN:

64278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

9.79e-7

AC:

AN:

1021264

Other (OTH)

AF:

0.0000196

AC:

AN:

51060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000174

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

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.039

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

PhyloP100

2.5

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.78

REVEL

Benign

0.037

Sift

Benign

0.32

Sift4G

Benign

0.38

Polyphen

0.011

Vest4

0.12

MutPred

0.57

Loss of sheet (P = 0.0104)

MVP

0.48

MPC

1.2

ClinPred

0.13

GERP RS

3.0

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.13

gMVP

0.34

Mutation Taster

=66/34

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over