Variant 8-143719060-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_139021.3(MAPK15):c.485T>A(p.Leu162Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,589,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 0 hom. )

Consequence

MAPK15
NM_139021.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK15	NM_139021.3 linkuse as main transcript	c.485T>A	p.Leu162Gln	missense_variant	6/14	ENST00000338033.9	NP_620590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK15	ENST00000338033.9 linkuse as main transcript	c.485T>A	p.Leu162Gln	missense_variant	6/14	1	NM_139021.3	ENSP00000337691	P1	Q8TD08-1
MAPK15	ENST00000395107.8 linkuse as main transcript	c.536T>A	p.Leu179Gln	missense_variant	6/8	1		ENSP00000378539		Q8TD08-3
MAPK15	ENST00000395108.2 linkuse as main transcript	c.485T>A	p.Leu162Gln	missense_variant	6/8	1		ENSP00000378540		Q8TD08-2
MAPK15	ENST00000484654.1 linkuse as main transcript	n.574T>A		non_coding_transcript_exon_variant	6/12	1

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000656

AC:

132

AN:

201298

Hom.:

AF XY:

0.000725

AC XY:

AN XY:

109016

show subpopulations

Gnomad AFR exome

AF:

0.0000834

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000760

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.000990

Gnomad OTH exome

AF:

0.000966

GnomAD4 exome

AF:

0.000800

AC:

1149

AN:

1436936

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

546

AN XY:

712826

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000723

Gnomad4 FIN exome

AF:

0.00259

Gnomad4 NFE exome

AF:

0.000851

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152258

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000548

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000697

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.485T>A (p.L162Q) alteration is located in exon 6 (coding exon 6) of the MAPK15 gene. This alteration results from a T to A substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.0

M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;T;D

Polyphen

1.0

D;.;.

Vest4

0.88

MVP

0.81

MPC

0.18

ClinPred

0.11

GERP RS

4.0

Varity_R

0.36

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.35

Position offset: 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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over