Variant chr8-143720286-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_139021.3(MAPK15):c.778C>T(p.Arg260Trp) variant causes a missense, splice region 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. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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
NM_139021.3 missense, splice_region

Scores

Splicing: ADA: 0.0002943

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

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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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK15	NM_139021.3 linkuse as main transcript	c.778C>T	p.Arg260Trp	missense_variant, splice_region_variant	8/14	ENST00000338033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK15	ENST00000338033.9 linkuse as main transcript	c.778C>T	p.Arg260Trp	missense_variant, splice_region_variant	8/14	1	NM_139021.3	P1	Q8TD08-1

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

GnomAD3 exomes

AF:

0.000890

AC:

183

AN:

205638

Hom.:

AF XY:

0.000886

AC XY:

AN XY:

110592

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 SAS exome

AF:

0.0000391

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

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.0000724

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.0000391

Gnomad4 NFE exome

AF:

0.000573

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152244

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000641

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.69

.;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.6

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.34

MVP

0.84

MPC

0.034

ClinPred

0.10

GERP RS

-2.0

Varity_R

0.33

gMVP

0.58

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over