Genetic Variant ENST00000395107.8:c.829C>T (chr8-143720286-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000395107.8(MAPK15):c.829C>T(p.Arg277Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,586,806 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 3 hom. )

Consequence

MAPK15
ENST00000395107.8 missense

Scores

Splicing: ADA: 0.0002943

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

Publications

6 publications found

Variant links:

Genes affected

MAPK15 (HGNC:24667): (mitogen-activated protein kinase 15) Enables MAP kinase activity and chromatin binding activity. Involved in several processes, including dopamine uptake; positive regulation of DNA metabolic process; and regulation of organelle organization. Located in several cellular components, including Golgi apparatus; autophagosome; and microtubule organizing center. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

MAPK15 links:

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new If you want to explore the variant's impact on the transcript ENST00000395107.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011644453).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395107.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK15	NM_139021.3	MANE Select	c.778C>T	p.Arg260Trp	missense splice_region	Exon 8 of 14	NP_620590.2	Q8TD08-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK15	ENST00000395107.8	TSL:1	c.829C>T	p.Arg277Trp	missense	Exon 8 of 8	ENSP00000378539.4	Q8TD08-3
MAPK15	ENST00000338033.9	TSL:1 MANE Select	c.778C>T	p.Arg260Trp	missense splice_region	Exon 8 of 14	ENSP00000337691.4	Q8TD08-1
MAPK15	ENST00000395108.2	TSL:1	c.722-262C>T		intron	N/A	ENSP00000378540.2	Q8TD08-2

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000890

AC:

183

AN:

205638

AF XY:

0.000886

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.0000985

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000561

Gnomad OTH exome

AF:

0.00173

GnomAD4 exome

AF:

0.000747

AC:

1071

AN:

1434562

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

558

AN XY:

710986

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33008

American (AMR)

AF:

0.0000724

AC:

AN:

41456

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

285

AN:

25344

East Asian (EAS)

AF:

0.00

AC:

AN:

38674

South Asian (SAS)

AF:

0.000256

AC:

AN:

81924

European-Finnish (FIN)

AF:

0.0000391

AC:

AN:

51206

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.000573

AC:

629

AN:

1098026

Other (OTH)

AF:

0.00127

AC:

AN:

59212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.00117

AC:

178

AN:

152244

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68012

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00121

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.8

PhyloP100

-2.8

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.6

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0010

Varity_R

0.33

gMVP

0.58

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.038

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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

Computational scores

Splicing

Publications

Other links and lift over