rs9483947

Variant names:

• chr6-136784262-C-T
• rs9483947
• NM_005923.4:c.448+7448G>A

Variant summary

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

The NM_005923.4(MAP3K5):​c.448+7448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,118 control chromosomes in the GnomAD database, including 29,824 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 0.63 (29824 hom., cov: 33)
• Consequence: MAP3K5 NM_005923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 10 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-AS2 (HGNC:56125): (MAP3K5 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.666 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.448+7448G>A		intron	N/A	NP_005914.1	Q99683-1
	MAP3K5	NM_001438058.1		c.775+7448G>A		intron	N/A	NP_001424987.1	A0A8V8TMH5
	MAP3K5	NM_001438579.1		c.6+7448G>A		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.448+7448G>A		intron	N/A	ENSP00000351908.4	Q99683-1
	MAP3K5	ENST00000698928.1		c.775+7448G>A		intron	N/A	ENSP00000514039.1	A0A8V8TMH5
	MAP3K5	ENST00000954598.1		c.448+7448G>A		intron	N/A	ENSP00000624657.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95021 AN: 152000 Hom.: 29807 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.625 AC: 95080 AN: 152118 Hom.: 29824 Cov.: 33 AF XY: 0.623 AC XY: 46352 AN XY: 74352

African (AFR) AF: 0.634 AC: 26324 AN: 41492

American (AMR) AF: 0.677 AC: 10354 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2287 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2930 AN: 5168

South Asian (SAS) AF: 0.617 AC: 2977 AN: 4826

European-Finnish (FIN) AF: 0.560 AC: 5911 AN: 10562

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42413 AN: 68004

Other (OTH) AF: 0.611 AC: 1289 AN: 2108

Alfa AF: 0.624 Hom.: 51587

Bravo AF: 0.632

Asia WGS AF: 0.647 AC: 2251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.010
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: rs9483947; hg19: chr6-137105400;