Genetic Variant MAP3K10:p.Phe606Phe (chr19-40213169-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002446.4(MAP3K10):c.1818T>C(p.Phe606Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,582,998 control chromosomes in the GnomAD database, including 428,731 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 0.75 ( 43064 hom., cov: 33)

Exomes 𝑓: 0.73 ( 385667 hom. )

Consequence

MAP3K10
NM_002446.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.279

Publications

24 publications found

Variant links:

Genes affected

MAP3K10 (HGNC:6849): (mitogen-activated protein kinase kinase kinase 10) The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008]

MAP3K10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP7

Synonymous conserved (PhyloP=-0.279 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K10	NM_002446.4 link	c.1818T>C	p.Phe606Phe	synonymous_variant	Exon 8 of 10	ENST00000253055.8	NP_002437.2	Q02779

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K10	ENST00000253055.8 link	c.1818T>C	p.Phe606Phe	synonymous_variant	Exon 8 of 10	1	NM_002446.4	ENSP00000253055.2		Q02779

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114089

AN:

152016

Hom.:

43030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.807

Gnomad AMI

AF:

0.808

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.777

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.729

Gnomad OTH

AF:

0.742

GnomAD2 exomes

AF:

0.733

AC:

147839

AN:

201660

AF XY:

0.732

show subpopulations

Gnomad AFR exome

AF:

0.804

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.727

GnomAD4 exome

AF:

0.734

AC:

1049765

AN:

1430864

Hom.:

385667

Cov.:

AF XY:

0.734

AC XY:

519942

AN XY:

708630

show subpopulations

African (AFR)

AF:

0.806

AC:

26755

AN:

33186

American (AMR)

AF:

0.764

AC:

29198

AN:

38198

Ashkenazi Jewish (ASJ)

AF:

0.633

AC:

16031

AN:

25326

East Asian (EAS)

AF:

0.683

AC:

26525

AN:

38818

South Asian (SAS)

AF:

0.772

AC:

63020

AN:

81624

European-Finnish (FIN)

AF:

0.700

AC:

35635

AN:

50930

Middle Eastern (MID)

AF:

0.725

AC:

4137

AN:

5706

European-Non Finnish (NFE)

AF:

0.733

AC:

804648

AN:

1097620

Other (OTH)

AF:

0.737

AC:

43816

AN:

59456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14471

28942

43414

57885

72356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19960

39920

59880

79840

99800

<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:

0.751

AC:

114188

AN:

152134

Hom.:

43064

Cov.:

AF XY:

0.748

AC XY:

55594

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.807

AC:

33510

AN:

41536

American (AMR)

AF:

0.764

AC:

11691

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2232

AN:

3470

East Asian (EAS)

AF:

0.693

AC:

3556

AN:

5134

South Asian (SAS)

AF:

0.776

AC:

3742

AN:

4820

European-Finnish (FIN)

AF:

0.696

AC:

7368

AN:

10592

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.729

AC:

49576

AN:

67970

Other (OTH)

AF:

0.741

AC:

1564

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1498

2995

4493

5990

7488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.734

Hom.:

36762

Bravo

AF:

0.757

Asia WGS

AF:

0.743

AC:

2585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.5

(source)

DANN

Benign

0.79

PhyloP100

-0.28

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