dbSNP rs6489818: MAPKAPK5:c.579+1596G>A (chr12-111872776-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003668.4(MAPKAPK5):c.579+1596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,960 control chromosomes in the GnomAD database, including 14,012 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 ( 14012 hom., cov: 32)

Consequence

MAPKAPK5
NM_003668.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

15 publications found

Variant links:

Genes affected

MAPKAPK5 (HGNC:6889): (MAPK activated protein kinase 5) The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]

MAPKAPK5 Gene-Disease associations (from GenCC):

neurocardiofaciodigital syndrome
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

MAPKAPK5 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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPKAPK5	NM_003668.4 link	c.579+1596G>A		intron_variant	Intron 7 of 13	ENST00000550735.7	NP_003659.2	Q8IW41-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAPKAPK5	ENST00000550735.7 link	c.579+1596G>A	intron_variant	Intron 7 of 13	1	NM_003668.4	ENSP00000449667.2	Q8IW41-2
MAPKAPK5	ENST00000551404.7 link	c.579+1596G>A	intron_variant	Intron 7 of 13	5		ENSP00000449381.2	Q8IW41-1
MAPKAPK5	ENST00000549875.1 link	c.132+1596G>A	intron_variant	Intron 2 of 8	5		ENSP00000473467.1	R4GN33
MAPKAPK5	ENST00000553053.5 link	n.132+1596G>A	intron_variant	Intron 2 of 6	5		ENSP00000448408.2	F8VRP2

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53837

AN:

151842

Hom.:

13972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.0987

Gnomad EAS

AF:

0.853

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.355

AC:

53939

AN:

151960

Hom.:

14012

Cov.:

AF XY:

0.355

AC XY:

26374

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.681

AC:

28212

AN:

41446

American (AMR)

AF:

0.336

AC:

5129

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0987

AC:

342

AN:

3466

East Asian (EAS)

AF:

0.853

AC:

4400

AN:

5158

South Asian (SAS)

AF:

0.295

AC:

1418

AN:

4810

European-Finnish (FIN)

AF:

0.155

AC:

1641

AN:

10556

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11862

AN:

67946

Other (OTH)

AF:

0.331

AC:

700

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1294

2589

3883

5178

6472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.276

Hom.:

1645

Bravo

AF:

0.389

Asia WGS

AF:

0.525

AC:

1823

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.93

(source)

DANN

Benign

0.17

PhyloP100

-1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over