Genetic Variant DUSP12:p.Cys23Tyr (chr1-161749869-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007240.3(DUSP12):c.68G>A(p.Cys23Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. C23S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DUSP12
NM_007240.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.853

Publications

0 publications found

Variant links:

Genes affected

DUSP12 (HGNC:3067): (dual specificity phosphatase 12) 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 is 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 is the human ortholog of the Saccharomyces cerevisiae YVH1 protein tyrosine phosphatase. It is localized predominantly in the nucleus, and is novel in that it contains, and is regulated by a zinc finger domain. [provided by RefSeq, Jul 2008]

DUSP12 links:

ATF6-DT (HGNC:55826): (ATF6 divergent transcript)

ATF6-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06683615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007240.3. 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
	DUSP12	NM_007240.3	MANE Select	c.68G>A	p.Cys23Tyr	missense	Exon 1 of 6	NP_009171.1	Q9UNI6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DUSP12	ENST00000367943.5	TSL:1 MANE Select	c.68G>A	p.Cys23Tyr	missense	Exon 1 of 6	ENSP00000356920.4	Q9UNI6
DUSP12	ENST00000931531.1		c.68G>A	p.Cys23Tyr	missense	Exon 1 of 7	ENSP00000601590.1
DUSP12	ENST00000954828.1		c.68G>A	p.Cys23Tyr	missense	Exon 1 of 7	ENSP00000624887.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33390

American (AMR)

AF:

0.00

AC:

AN:

44258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39500

South Asian (SAS)

AF:

0.00

AC:

AN:

85858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110652

Other (OTH)

AF:

0.0000166

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.083

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.40

M_CAP

Benign

0.0026

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.69

PhyloP100

-0.85

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.47

REVEL

Benign

0.023

Sift

Benign

0.048

Sift4G

Uncertain

0.033

Polyphen

0.14

Vest4

0.29

MutPred

0.33

Gain of phosphorylation at C23 (P = 0.0148)

MVP

0.14

MPC

0.51

ClinPred

0.80

GERP RS

-4.2

PromoterAI

0.054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.50

Mutation Taster

=99/1

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