rs10484491

Variant names:

• chr6-136706729-A-G
• rs10484491
• NM_005923.4:c.589-1596T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-136706729-A-G
• chr6-136706729-A-T

Variant summary

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

The NM_005923.4(MAP3K5):​c.589-1596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,084 control chromosomes in the GnomAD database, including 25,924 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 0.57 (25924 hom., cov: 32)
• Consequence: MAP3K5 NM_005923.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K5	NM_005923.4	c.589-1596T>C		intron_variant	Intron 2 of 29	ENST00000359015.5	NP_005914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K5	ENST00000359015.5	c.589-1596T>C		intron_variant	Intron 2 of 29	1	NM_005923.4	ENSP00000351908.4
MAP3K5	ENST00000698928.1	c.916-1596T>C		intron_variant	Intron 3 of 30			ENSP00000514039.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86646 AN: 151966 Hom.: 25883 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.570 AC: 86751 AN: 152084 Hom.: 25924 Cov.: 32 AF XY: 0.569 AC XY: 42318 AN XY: 74356

African (AFR) AF: 0.746 AC: 30928 AN: 41478

American (AMR) AF: 0.613 AC: 9380 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2864 AN: 5164

South Asian (SAS) AF: 0.627 AC: 3020 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4394 AN: 10584

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32641 AN: 67966

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

Alfa AF: 0.451 Hom.: 2091

Bravo AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.035
DANN	Benign	0.37
PhyloP100		-1.9
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: rs10484491; hg19: chr6-137027867; COSMIC: COSV62891886;