chr10-30444564-A-G

Position:

• chr10-30444564-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

MAP3K8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K8	NM_005204.4	c.337-3218A>G		intron_variant		ENST00000263056.6	NP_005195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K8	ENST00000263056.6	c.337-3218A>G		intron_variant		1	NM_005204.4	ENSP00000263056.1

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

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.623

Alfa AF: 0.614 Hom.: 4496

Bravo AF: 0.638

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.82
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs303438; hg19: chr10-30733493;