rs1042058

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 1174756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-30439172-T-C is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.513

AC:

129081

AN:

251414

Hom.:

35707

AF XY:

0.513

AC XY:

69758

AN XY:

135902

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 SAS exome

AF:

0.355

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

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.522

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.612

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.452

AC:

68774

AN:

152096

Hom.:

18559

Cov.:

AF XY:

0.450

AC XY:

33465

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.601

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.567

Hom.:

59227

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

DANN

Benign

0.38

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

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