dbSNP rs7698: MAPK3:c.*262C>T (chr16-30114479-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_002746.3(MAPK3):c.*262C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 148,036 control chromosomes in the GnomAD database, including 805 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 0.093 ( 800 hom., cov: 31)

Exomes 𝑓: 0.075 ( 5 hom. )

Consequence

MAPK3
NM_002746.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.695

Publications

11 publications found

Variant links:

Genes affected

MAPK3 (HGNC:6877): (mitogen-activated protein kinase 3) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]

MAPK3 links:

ENSG00000300821 (HGNC:):

ENSG00000300821 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MAPK3	NM_002746.3 link	c.*262C>T	3_prime_UTR_variant	Exon 9 of 9	ENST00000263025.9	NP_002737.2
MAPK3	XR_243293.2 link	n.1464C>T	non_coding_transcript_exon_variant	Exon 10 of 10
MAPK3	NM_001109891.2 link	c.*262C>T	3_prime_UTR_variant	Exon 8 of 8		NP_001103361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK3	ENST00000263025.9 link	c.*262C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002746.3	ENSP00000263025.4

Frequencies

GnomAD3 genomes

AF:

0.0935

AC:

13754

AN:

147166

Hom.:

798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.0913

Gnomad AMR

AF:

0.0834

Gnomad ASJ

AF:

0.0788

Gnomad EAS

AF:

0.00166

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.0780

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0749

AC:

AN:

748

Hom.:

Cov.:

AF XY:

0.0813

AC XY:

AN XY:

504

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0486

AC:

AN:

432

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.114

AC:

AN:

264

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0934

AC:

13763

AN:

147288

Hom.:

800

Cov.:

AF XY:

0.0896

AC XY:

6448

AN XY:

71938

show subpopulations

African (AFR)

AF:

0.156

AC:

6179

AN:

39616

American (AMR)

AF:

0.0832

AC:

1250

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.0788

AC:

270

AN:

3428

East Asian (EAS)

AF:

0.00167

AC:

AN:

4804

South Asian (SAS)

AF:

0.0321

AC:

144

AN:

4492

European-Finnish (FIN)

AF:

0.0382

AC:

376

AN:

9834

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0780

AC:

5213

AN:

66844

Other (OTH)

AF:

0.100

AC:

206

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

609

1218

1828

2437

3046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0885

Hom.:

935

Bravo

AF:

0.0998

Asia WGS

AF:

0.0260

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.5

(source)

DANN

Benign

0.63

PhyloP100

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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