chr10-30444564-A-G

Variant names:

• chr10-30444564-A-G
• rs303438
• NM_005204.4:c.337-3218A>G

Variant summary

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

The NM_005204.4(MAP3K8):​c.337-3218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,062 control chromosomes in the GnomAD database, including 31,488 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 0.64 (31488 hom., cov: 32)
• Consequence: MAP3K8 NM_005204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005204.4. 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
	MAP3K8	NM_005204.4	MANE Select	c.337-3218A>G		intron	N/A	NP_005195.2
	MAP3K8	NM_001244134.1		c.337-3218A>G		intron	N/A	NP_001231063.1	P41279-1
	MAP3K8	NM_001320961.2		c.337-3218A>G		intron	N/A	NP_001307890.1	P41279-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K8	ENST00000263056.6	TSL:1 MANE Select	c.337-3218A>G		intron	N/A	ENSP00000263056.1	P41279-1
	MAP3K8	ENST00000375321.1	TSL:1	c.337-3218A>G		intron	N/A	ENSP00000364470.1	P41279-1
	MAP3K8	ENST00000542547.5	TSL:1	c.337-3218A>G		intron	N/A	ENSP00000443610.1	P41279-1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97189 AN: 151944 Hom.: 31482 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.639 AC: 97237 AN: 152062 Hom.: 31488 Cov.: 32 AF XY: 0.633 AC XY: 47049 AN XY: 74326

African (AFR) AF: 0.671 AC: 27831 AN: 41472

American (AMR) AF: 0.607 AC: 9269 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2291 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2064 AN: 5180

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4816

European-Finnish (FIN) AF: 0.675 AC: 7121 AN: 10552

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44825 AN: 67976

Other (OTH) AF: 0.623 AC: 1316 AN: 2112

Alfa AF: 0.617 Hom.: 9474

Bravo AF: 0.638

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.69
PhyloP100		-0.047
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: rs303438; hg19: chr10-30733493;