Variant 6-136642511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_005923.4(MAP3K5):c.1838+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,599,564 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 87 hom. )

Consequence

MAP3K5
NM_005923.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223

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:

MAP3K5-AS1 (HGNC:40358): (MAP3K5 antisense RNA 1)

MAP3K5-AS1 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=-0.46).

BP6

Variant 6-136642511-G-A is Benign according to our data. Variant chr6-136642511-G-A is described in ClinVar as [Benign]. Clinvar id is 775243.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 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.1838+9C>T		intron_variant		ENST00000359015.5	NP_005914.1
MAP3K5-AS1	NR_125858.1 linkuse as main transcript	n.336-5261G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MAP3K5	ENST00000359015.5 linkuse as main transcript	c.1838+9C>T	intron_variant	1	NM_005923.4	ENSP00000351908	P1	Q99683-1
MAP3K5-AS1	ENST00000432477.2 linkuse as main transcript	n.384-5261G>A	intron_variant, non_coding_transcript_variant	2
MAP3K5	ENST00000698928.1 linkuse as main transcript	c.2165+9C>T	intron_variant			ENSP00000514039

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2923

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0663

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00819

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00522

AC:

1308

AN:

250534

Hom.:

AF XY:

0.00405

AC XY:

548

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.0689

Gnomad AMR exome

AF:

0.00378

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00214

AC:

3094

AN:

1447410

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

1387

AN XY:

721102

show subpopulations

Gnomad4 AFR exome

AF:

0.0706

Gnomad4 AMR exome

AF:

0.00429

Gnomad4 ASJ exome

AF:

0.0000768

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.0192

AC:

2928

AN:

152154

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1400

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0662

Gnomad4 AMR

AF:

0.00818

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00867

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000652

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.71

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