NM_005923.4:c.2016+799A>G

Variant names:

• chr6-136636526-T-C
• rs2064205
• NM_005923.4:c.2016+799A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005923.4(MAP3K5):​c.2016+799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,102 control chromosomes in the GnomAD database, including 37,493 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 0.69 (37493 hom., cov: 32)
• Consequence: MAP3K5 NM_005923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K5	NM_005923.4	MANE Select	c.2016+799A>G		intron	N/A	NP_005914.1	Q99683-1
	MAP3K5	NM_001438058.1		c.2343+799A>G		intron	N/A	NP_001424987.1	A0A8V8TMH5
	MAP3K5	NM_001438579.1		c.1434+799A>G		intron	N/A	NP_001425508.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K5	ENST00000359015.5	TSL:1 MANE Select	c.2016+799A>G		intron	N/A	ENSP00000351908.4	Q99683-1
	MAP3K5	ENST00000698928.1		c.2343+799A>G		intron	N/A	ENSP00000514039.1	A0A8V8TMH5
	MAP3K5	ENST00000954598.1		c.2085+799A>G		intron	N/A	ENSP00000624657.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105367 AN: 151984 Hom.: 37454 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.693 AC: 105458 AN: 152102 Hom.: 37493 Cov.: 32 AF XY: 0.689 AC XY: 51225 AN XY: 74356

African (AFR) AF: 0.848 AC: 35206 AN: 41500

American (AMR) AF: 0.678 AC: 10354 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3472

East Asian (EAS) AF: 0.712 AC: 3680 AN: 5166

South Asian (SAS) AF: 0.716 AC: 3455 AN: 4824

European-Finnish (FIN) AF: 0.542 AC: 5730 AN: 10576

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42434 AN: 67976

Other (OTH) AF: 0.693 AC: 1460 AN: 2106

Alfa AF: 0.673 Hom.: 6316

Bravo AF: 0.708

Asia WGS AF: 0.723 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2064205; hg19: chr6-136957664;