10-30439172-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005204.4(MAP3K8):c.234T>C(p.Tyr78Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,878 control chromosomes in the GnomAD database, including 263,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 18559 hom., cov: 33)

Exomes 𝑓: 0.57 ( 244930 hom. )

Consequence

MAP3K8
NM_005204.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.69

Publications

76 publications found

Variant links:

Genes affected

MAP3K8 (HGNC:6860): (mitogen-activated protein kinase kinase kinase 8) This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

MAP3K8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-30439172-T-C is Benign according to our data. Variant chr10-30439172-T-C is described in ClinVar as Benign. ClinVar VariationId is 1174756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K8	NM_005204.4 link	c.234T>C	p.Tyr78Tyr	synonymous_variant	Exon 3 of 9	ENST00000263056.6	NP_005195.2	P41279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K8	ENST00000263056.6 link	c.234T>C	p.Tyr78Tyr	synonymous_variant	Exon 3 of 9	1	NM_005204.4	ENSP00000263056.1		P41279-1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68768

AN:

151978

Hom.:

18567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.476

GnomAD2 exomes

AF:

0.513

AC:

129081

AN:

251414

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.541

GnomAD4 exome

AF:

0.570

AC:

833223

AN:

1461782

Hom.:

244930

Cov.:

AF XY:

0.565

AC XY:

410633

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.136

AC:

4540

AN:

33480

American (AMR)

AF:

0.536

AC:

23957

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

13654

AN:

26134

East Asian (EAS)

AF:

0.405

AC:

16097

AN:

39698

South Asian (SAS)

AF:

0.359

AC:

30993

AN:

86254

European-Finnish (FIN)

AF:

0.612

AC:

32686

AN:

53420

Middle Eastern (MID)

AF:

0.446

AC:

2571

AN:

5768

European-Non Finnish (NFE)

AF:

0.608

AC:

676250

AN:

1111912

Other (OTH)

AF:

0.538

AC:

32475

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

20107

40213

60320

80426

100533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17948

35896

53844

71792

89740

<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:

0.452

AC:

68774

AN:

152096

Hom.:

18559

Cov.:

AF XY:

0.450

AC XY:

33465

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.155

AC:

6435

AN:

41526

American (AMR)

AF:

0.515

AC:

7866

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1773

AN:

3470

East Asian (EAS)

AF:

0.370

AC:

1909

AN:

5162

South Asian (SAS)

AF:

0.331

AC:

1598

AN:

4824

European-Finnish (FIN)

AF:

0.601

AC:

6350

AN:

10558

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.606

AC:

41178

AN:

67962

Other (OTH)

AF:

0.476

AC:

1003

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1649

3298

4948

6597

8246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.551

Hom.:

114267

Bravo

AF:

0.432

Asia WGS

AF:

0.347

AC:

1207

AN:

3478

EpiCase

AF:

0.590

EpiControl

AF:

0.588

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.16

(source)

DANN

Benign

0.38

PhyloP100

-2.7

PromoterAI

0.014

Neutral

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over