Genetic Variant MAPK12:p.Pro61Pro (chr22-50261239-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_002969.6(MAPK12):c.183T>C(p.Pro61Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,575,850 control chromosomes in the GnomAD database, including 451,117 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 0.74 ( 41467 hom., cov: 33)

Exomes 𝑓: 0.76 ( 409650 hom. )

Consequence

MAPK12
NM_002969.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

31 publications found

Variant links:

Genes affected

MAPK12 (HGNC:6874): (mitogen-activated protein kinase 12) Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

MAPK12 links:

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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=-0.49).

BP7

Synonymous conserved (PhyloP=0.207 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK12	NM_002969.6 link	c.183T>C	p.Pro61Pro	synonymous_variant	Exon 2 of 12	ENST00000215659.13	NP_002960.2	P53778-1
MAPK12	NM_001303252.3 link	c.183T>C	p.Pro61Pro	synonymous_variant	Exon 2 of 11		NP_001290181.1	P53778-2Q6N076

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK12	ENST00000215659.13 link	c.183T>C	p.Pro61Pro	synonymous_variant	Exon 2 of 12	1	NM_002969.6	ENSP00000215659.8		P53778-1

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

111827

AN:

151804

Hom.:

41428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.770

Gnomad OTH

AF:

0.759

GnomAD2 exomes

AF:

0.738

AC:

140898

AN:

190900

AF XY:

0.737

show subpopulations

Gnomad AFR exome

AF:

0.685

Gnomad AMR exome

AF:

0.733

Gnomad ASJ exome

AF:

0.761

Gnomad EAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.826

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.758

GnomAD4 exome

AF:

0.757

AC:

1078010

AN:

1423928

Hom.:

409650

Cov.:

AF XY:

0.756

AC XY:

533817

AN XY:

706250

show subpopulations

African (AFR)

AF:

0.674

AC:

20883

AN:

30976

American (AMR)

AF:

0.732

AC:

29984

AN:

40936

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

19270

AN:

25280

East Asian (EAS)

AF:

0.608

AC:

22129

AN:

36410

South Asian (SAS)

AF:

0.666

AC:

54156

AN:

81340

European-Finnish (FIN)

AF:

0.817

AC:

40614

AN:

49694

Middle Eastern (MID)

AF:

0.756

AC:

4279

AN:

5660

European-Non Finnish (NFE)

AF:

0.770

AC:

842929

AN:

1094838

Other (OTH)

AF:

0.744

AC:

43766

AN:

58794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12721

25442

38164

50885

63606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20248

40496

60744

80992

101240

<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:

0.737

AC:

111926

AN:

151922

Hom.:

41467

Cov.:

AF XY:

0.737

AC XY:

54712

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.683

AC:

28309

AN:

41462

American (AMR)

AF:

0.733

AC:

11207

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

2667

AN:

3472

East Asian (EAS)

AF:

0.574

AC:

2940

AN:

5124

South Asian (SAS)

AF:

0.654

AC:

3160

AN:

4830

European-Finnish (FIN)

AF:

0.828

AC:

8732

AN:

10552

Middle Eastern (MID)

AF:

0.760

AC:

222

AN:

292

European-Non Finnish (NFE)

AF:

0.770

AC:

52275

AN:

67882

Other (OTH)

AF:

0.761

AC:

1606

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1507

3015

4522

6030

7537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.757

Hom.:

19895

Bravo

AF:

0.732

Asia WGS

AF:

0.692

AC:

2400

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.21

PromoterAI

-0.073

Neutral

(source)

Mutation Taster

=293/7

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