dbSNP rs958: MAPK10:n.*1411G>A (chr4-86016721-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000310816.8(MAPK10):n.*1411G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 157,020 control chromosomes in the GnomAD database, including 3,289 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 0.20 ( 3179 hom., cov: 32)

Exomes 𝑓: 0.18 ( 110 hom. )

Consequence

MAPK10
ENST00000310816.8 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

Publications

17 publications found

Variant links:

Genes affected

MAPK10 (HGNC:6872): (mitogen-activated protein kinase 10) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

MAPK10 Gene-Disease associations (from GenCC):

Lennox-Gastaut syndrome
Inheritance: AD Classification: LIMITED Submitted by: G2P

MAPK10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK10	NM_138982.4 link	c.*507G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000641462.2	NP_620448.1	P53779-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK10	ENST00000641462.2 link	c.*507G>A		3_prime_UTR_variant	Exon 14 of 14		NM_138982.4	ENSP00000493435.1		P53779-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30322

AN:

151912

Hom.:

3175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.181

AC:

904

AN:

4990

Hom.:

110

Cov.:

AF XY:

0.179

AC XY:

480

AN XY:

2680

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.129

AC:

154

AN:

1194

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

AN:

East Asian (EAS)

AF:

0.213

AC:

AN:

122

South Asian (SAS)

AF:

0.204

AC:

AN:

416

European-Finnish (FIN)

AF:

0.152

AC:

AN:

138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.196

AC:

563

AN:

2872

Other (OTH)

AF:

0.247

AC:

AN:

174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.200

AC:

30346

AN:

152030

Hom.:

3179

Cov.:

AF XY:

0.199

AC XY:

14768

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.197

AC:

8149

AN:

41428

American (AMR)

AF:

0.201

AC:

3071

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

766

AN:

3468

East Asian (EAS)

AF:

0.256

AC:

1322

AN:

5170

South Asian (SAS)

AF:

0.245

AC:

1181

AN:

4812

European-Finnish (FIN)

AF:

0.127

AC:

1342

AN:

10576

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13855

AN:

67960

Other (OTH)

AF:

0.217

AC:

459

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1256

2512

3767

5023

6279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.201

Hom.:

4188

Bravo

AF:

0.200

Asia WGS

AF:

0.247

AC:

860

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.86

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