dbSNP rs11130254: MAPKAPK3:c.*721A>C (chr3-50648767-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001243925.2(MAPKAPK3):c.*721A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,320 control chromosomes in the GnomAD database, including 682 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 0.080 ( 682 hom., cov: 34)

Exomes 𝑓: 0.059 ( 0 hom. )

Consequence

MAPKAPK3
NM_001243925.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.912

Publications

20 publications found

Variant links:

Genes affected

MAPKAPK3 (HGNC:6888): (MAPK activated protein kinase 3) This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

MAPKAPK3 Gene-Disease associations (from GenCC):

patterned macular dystrophy 3
Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

MAPKAPK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK3	NM_001243925.2 link	c.*721A>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000621469.5	NP_001230854.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MAPKAPK3	ENST00000621469.5 link	c.*721A>C	3_prime_UTR_variant	Exon 11 of 11	1	NM_001243925.2	ENSP00000478922.1
MAPKAPK3	ENST00000357955.6 link	c.*721A>C	3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000350639.2
MAPKAPK3	ENST00000446044.5 link	c.*721A>C	3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000396467.1
MAPKAPK3	ENST00000451680.1 link	c.*721A>C	downstream_gene_variant		2		ENSP00000394894.1

Frequencies

GnomAD3 genomes

AF:

0.0802

AC:

12200

AN:

152168

Hom.:

682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0747

GnomAD4 exome

AF:

0.0588

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

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

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

AF:

0.0801

AC:

12201

AN:

152286

Hom.:

682

Cov.:

AF XY:

0.0797

AC XY:

5934

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0231

AC:

960

AN:

41582

American (AMR)

AF:

0.0707

AC:

1082

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0386

AC:

134

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0147

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.133

AC:

1408

AN:

10606

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8243

AN:

68012

Other (OTH)

AF:

0.0739

AC:

156

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

600

1200

1800

2400

3000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.101

Hom.:

1574

Bravo

AF:

0.0728

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

(source)

DANN

Benign

0.51

PhyloP100

0.91

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