Variant 6-136622925-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005923.4(MAP3K5):c.2073T>C(p.Tyr691Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 1,603,288 control chromosomes in the GnomAD database, including 4,644 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 0.094 ( 1704 hom., cov: 32)

Exomes 𝑓: 0.023 ( 2940 hom. )

Consequence

MAP3K5
NM_005923.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Variant links:

Genes affected

MAP3K5 (HGNC:6857): (mitogen-activated protein kinase kinase kinase 5) Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

MAP3K5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K5	NM_005923.4 linkuse as main transcript	c.2073T>C	p.Tyr691Tyr	synonymous_variant	15/30	ENST00000359015.5	NP_005914.1	Q99683-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K5	ENST00000359015.5 linkuse as main transcript	c.2073T>C	p.Tyr691Tyr	synonymous_variant	15/30	1	NM_005923.4	ENSP00000351908.4		Q99683-1
MAP3K5	ENST00000698928.1 linkuse as main transcript	c.2400T>C	p.Tyr800Tyr	synonymous_variant	16/31			ENSP00000514039.1		A0A8V8TMH5

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

14277

AN:

151780

Hom.:

1687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.00616

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00518

Gnomad OTH

AF:

0.0817

GnomAD3 exomes

AF:

0.0577

AC:

14500

AN:

251412

Hom.:

1460

AF XY:

0.0472

AC XY:

6417

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.00694

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00638

Gnomad NFE exome

AF:

0.00477

Gnomad OTH exome

AF:

0.0349

GnomAD4 exome

AF:

0.0230

AC:

33435

AN:

1451390

Hom.:

2940

Cov.:

AF XY:

0.0215

AC XY:

15495

AN XY:

722272

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.00656

Gnomad4 EAS exome

AF:

0.243

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.00619

Gnomad4 NFE exome

AF:

0.00430

Gnomad4 OTH exome

AF:

0.0379

GnomAD4 genome

AF:

0.0945

AC:

14348

AN:

151898

Hom.:

1704

Cov.:

AF XY:

0.0939

AC XY:

6976

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.0983

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.00616

Gnomad4 NFE

AF:

0.00517

Gnomad4 OTH

AF:

0.0851

Alfa

AF:

0.0248

Hom.:

816

Bravo

AF:

0.112

Asia WGS

AF:

0.140

AC:

486

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.054

DANN

Benign

0.34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over