Variant chr6-136592478-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005923.4(MAP3K5):c.3015C>T(p.Cys1005=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,878 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00084 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 14 hom. )

Consequence

MAP3K5
NM_005923.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.146

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 6-136592478-G-A is Benign according to our data. Variant chr6-136592478-G-A is described in ClinVar as [Benign]. Clinvar id is 734375.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.146 with no splicing effect.

BS2

High AC in GnomAd4 at 128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K5	NM_005923.4 linkuse as main transcript	c.3015C>T	p.Cys1005=	synonymous_variant	22/30	ENST00000359015.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K5	ENST00000359015.5 linkuse as main transcript	c.3015C>T	p.Cys1005=	synonymous_variant	22/30	1	NM_005923.4	P1	Q99683-1
MAP3K5	ENST00000698928.1 linkuse as main transcript	c.3342C>T	p.Cys1114=	synonymous_variant	23/31

Frequencies

GnomAD3 genomes

AF:

0.000856

AC:

130

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00789

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00174

AC:

438

AN:

251376

Hom.:

AF XY:

0.00212

AC XY:

288

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00921

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00136

AC:

1985

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1148

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00865

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000967

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.000842

AC:

128

AN:

152010

Hom.:

Cov.:

AF XY:

0.000861

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00769

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000793

Hom.:

Bravo

AF:

0.000665

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.32

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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