Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_138982.4(MAPK10):c.339C>T(p.Val113Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.0011 in 1,613,020 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 9 hom. )

Consequence

MAPK10
NM_138982.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.70

Publications

1 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.088).

BP6

Variant 4-86107250-G-A is Benign according to our data. Variant chr4-86107250-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00536 (815/152190) while in subpopulation AFR AF = 0.0184 (765/41520). AF 95% confidence interval is 0.0173. There are 8 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 815 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAPK10	NM_138982.4	MANE Select	c.339C>T	p.Val113Val	synonymous	Exon 5 of 14	NP_620448.1
MAPK10	NM_001318069.2		c.339C>T	p.Val113Val	synonymous	Exon 5 of 14	NP_001304998.1
MAPK10	NM_001318067.1		c.339C>T	p.Val113Val	synonymous	Exon 4 of 13	NP_001304996.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAPK10	ENST00000641462.2	MANE Select	c.339C>T	p.Val113Val	synonymous	Exon 5 of 14	ENSP00000493435.1
MAPK10	ENST00000638225.1	TSL:1	c.225C>T	p.Val75Val	synonymous	Exon 5 of 14	ENSP00000491866.1
MAPK10	ENST00000395160.9	TSL:1	c.339C>T	p.Val113Val	synonymous	Exon 5 of 14	ENSP00000378589.5

Frequencies

GnomAD3 genomes

AF:

0.00536

AC:

815

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00138

AC:

347

AN:

250560

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000656

AC:

958

AN:

1460830

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

439

AN XY:

726718

show subpopulations

African (AFR)

AF:

0.0193

AC:

646

AN:

33400

American (AMR)

AF:

0.00114

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000150

AC:

167

AN:

1111330

Other (OTH)

AF:

0.00128

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00536

AC:

815

AN:

152190

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0184

AC:

765

AN:

41520

American (AMR)

AF:

0.00118

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68020

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00610

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000546

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

3.7

Mutation Taster

=127/173

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs28760360

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over