Genetic Variant NM_004419.4:c.139C>A (chr10-110498260-C-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_004419.4(DUSP5):c.139C>A(p.Leu47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,350,384 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. L47P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

DUSP5
NM_004419.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.950

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40557402).

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.139C>A	p.Leu47Ile	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.139C>A	p.Leu47Ile	missense	Exon 1 of 4	ENSP00000358596.3	Q16690
DUSP5	ENST00000925260.1		c.139C>A	p.Leu47Ile	missense	Exon 1 of 4	ENSP00000595319.1
DUSP5	ENST00000895745.1		c.139C>A	p.Leu47Ile	missense	Exon 1 of 2	ENSP00000565804.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1350384

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

672824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27750

American (AMR)

AF:

0.00

AC:

AN:

36944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22612

East Asian (EAS)

AF:

0.00

AC:

AN:

29808

South Asian (SAS)

AF:

0.00

AC:

AN:

79388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.00000189

AC:

AN:

1055522

Other (OTH)

AF:

0.00

AC:

AN:

54322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

0.30

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.6

PhyloP100

0.95

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.72

REVEL

Benign

0.15

Sift

Benign

0.21

Sift4G

Benign

0.40

Polyphen

0.86

Vest4

0.30

MutPred

0.39

Loss of helix (P = 0.079)

MVP

0.70

MPC

1.3

ClinPred

0.70

GERP RS

5.0

PromoterAI

0.065

Neutral

(source)

Varity_R

0.35

gMVP

0.34

Mutation Taster

=63/37

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