10-30460966-G-A

Position:

• chr10-30460966-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005204.4(MAP3K8):​c.*130G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,125,046 control chromosomes in the GnomAD database, including 427,774 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 0.89 (60159 hom., cov: 31)
  • Exomes 𝑓: 0.87 (367615 hom.)
• Consequence: MAP3K8 NM_005204.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K8	NM_005204.4	c.*130G>A		3_prime_UTR_variant	9/9	ENST00000263056.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K8	ENST00000263056.6	c.*130G>A		3_prime_UTR_variant	9/9	1	NM_005204.4	P1
MAP3K8	ENST00000375321.1	c.*130G>A		3_prime_UTR_variant	7/7	1		P1
MAP3K8	ENST00000542547.5	c.*130G>A		3_prime_UTR_variant	8/8	1		P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135065 AN: 152050 Hom.: 60092 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.868 AC: 844847 AN: 972878 Hom.: 367615 Cov.: 12 AF XY: 0.865 AC XY: 420637 AN XY: 486362

Gnomad4 AFR exome AF: 0.936

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.761

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.870

Gnomad4 OTH exome AF: 0.874

GnomAD4 genome AF: 0.888 AC: 135191 AN: 152168 Hom.: 60159 Cov.: 31 AF XY: 0.888 AC XY: 66047 AN XY: 74386

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.869

Alfa AF: 0.874 Hom.: 55805

Bravo AF: 0.892

Asia WGS AF: 0.874 AC: 3042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.47

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: rs3034; hg19: chr10-30749895;