rs306588

Variant names:

• chr10-30434664-G-A
• rs306588
• NM_005204.4:c.-255+286G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-30434664-G-A
• chr10-30434664-G-T

Variant summary

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

The NM_001320961.2(MAP3K8):​c.-108G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 985,396 control chromosomes in the GnomAD database, including 240,782 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 0.71 (39247 hom., cov: 34)
  • Exomes 𝑓: 0.69 (201535 hom.)
• Consequence: MAP3K8 NM_001320961.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 11 publications found

Genes affected

MAP3K8 (HGNC:6860): (mitogen-activated protein kinase kinase kinase 8) This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320961.2. 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
	MAP3K8	NM_005204.4	MANE Select	c.-255+286G>A		intron	N/A	NP_005195.2
	MAP3K8	NM_001320961.2		c.-108G>A		5_prime_UTR	Exon 1 of 8	NP_001307890.1	P41279-1
	MAP3K8	NM_001244134.1		c.-24+286G>A		intron	N/A	NP_001231063.1	P41279-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K8	ENST00000263056.6	TSL:1 MANE Select	c.-255+286G>A		intron	N/A	ENSP00000263056.1	P41279-1
	MAP3K8	ENST00000542547.5	TSL:1	c.-24+286G>A		intron	N/A	ENSP00000443610.1	P41279-1
	MAP3K8	ENST00000971343.1		c.-108G>A		5_prime_UTR	Exon 1 of 9	ENSP00000641402.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108443 AN: 152048 Hom.: 39207 Cov.: 34

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.694 AC: 578237 AN: 833230 Hom.: 201535 Cov.: 45 AF XY: 0.693 AC XY: 266717 AN XY: 384794

African (AFR) AF: 0.805 AC: 12709 AN: 15786

American (AMR) AF: 0.733 AC: 721 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 3656 AN: 5154

East Asian (EAS) AF: 0.512 AC: 1859 AN: 3632

South Asian (SAS) AF: 0.434 AC: 7142 AN: 16464

European-Finnish (FIN) AF: 0.683 AC: 194 AN: 284

Middle Eastern (MID) AF: 0.604 AC: 979 AN: 1620

European-Non Finnish (NFE) AF: 0.699 AC: 532446 AN: 762004

Other (OTH) AF: 0.679 AC: 18531 AN: 27302

GnomAD4 genome AF: 0.713 AC: 108540 AN: 152166 Hom.: 39247 Cov.: 34 AF XY: 0.706 AC XY: 52548 AN XY: 74386

African (AFR) AF: 0.801 AC: 33276 AN: 41526

American (AMR) AF: 0.709 AC: 10847 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2496 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2773 AN: 5166

South Asian (SAS) AF: 0.414 AC: 1999 AN: 4828

European-Finnish (FIN) AF: 0.692 AC: 7330 AN: 10590

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47519 AN: 67966

Other (OTH) AF: 0.715 AC: 1509 AN: 2110

Alfa AF: 0.717 Hom.: 5368

Bravo AF: 0.722

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		2.5
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs306588; hg19: chr10-30723593;