dbSNP rs1063178: DUSP12:p.Tyr170Tyr (chr1-161751917-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007240.3(DUSP12):c.510C>T(p.Tyr170Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,609,770 control chromosomes in the GnomAD database, including 93,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9292 hom., cov: 32)

Exomes 𝑓: 0.34 ( 84393 hom. )

Consequence

DUSP12
NM_007240.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.575

Publications

24 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=0.575 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP12	NM_007240.3 link	c.510C>T	p.Tyr170Tyr	synonymous_variant	Exon 3 of 6	ENST00000367943.5	NP_009171.1	Q9UNI6
DUSP12	XM_005244862.4 link	c.120C>T	p.Tyr40Tyr	synonymous_variant	Exon 3 of 6		XP_005244919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP12	ENST00000367943.5 link	c.510C>T	p.Tyr170Tyr	synonymous_variant	Exon 3 of 6	1	NM_007240.3	ENSP00000356920.4		Q9UNI6

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52696

AN:

151800

Hom.:

9287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.346

GnomAD2 exomes

AF:

0.335

AC:

84034

AN:

250490

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.337

AC:

490801

AN:

1457852

Hom.:

84393

Cov.:

AF XY:

0.338

AC XY:

244874

AN XY:

725348

show subpopulations

African (AFR)

AF:

0.388

AC:

12929

AN:

33348

American (AMR)

AF:

0.248

AC:

11070

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

8444

AN:

26056

East Asian (EAS)

AF:

0.497

AC:

19723

AN:

39664

South Asian (SAS)

AF:

0.344

AC:

29515

AN:

85860

European-Finnish (FIN)

AF:

0.303

AC:

16184

AN:

53342

Middle Eastern (MID)

AF:

0.401

AC:

2280

AN:

5682

European-Non Finnish (NFE)

AF:

0.334

AC:

370393

AN:

1109096

Other (OTH)

AF:

0.336

AC:

20263

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

15847

31695

47542

63390

79237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11980

23960

35940

47920

59900

<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:

0.347

AC:

52724

AN:

151918

Hom.:

9292

Cov.:

AF XY:

0.347

AC XY:

25751

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.385

AC:

15943

AN:

41426

American (AMR)

AF:

0.294

AC:

4476

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1131

AN:

3470

East Asian (EAS)

AF:

0.481

AC:

2485

AN:

5166

South Asian (SAS)

AF:

0.359

AC:

1725

AN:

4806

European-Finnish (FIN)

AF:

0.312

AC:

3279

AN:

10512

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.332

AC:

22575

AN:

67970

Other (OTH)

AF:

0.342

AC:

724

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1775

3551

5326

7102

8877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.339

Hom.:

39172

Bravo

AF:

0.346

Asia WGS

AF:

0.381

AC:

1323

AN:

3478

EpiCase

AF:

0.349

EpiControl

AF:

0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.3

(source)

DANN

Benign

0.46

PhyloP100

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over