rs3034

Variant names:

• chr10-30460966-G-A
• rs3034
• NM_005204.4:c.*130G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.9).
• 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 rank	MANE	Protein	UniProt
MAP3K8	NM_005204.4	c.*130G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000263056.6	NP_005195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K8	ENST00000263056.6	c.*130G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_005204.4	ENSP00000263056.1
MAP3K8	ENST00000375321.1	c.*130G>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000364470.1
MAP3K8	ENST00000542547.5	c.*130G>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000443610.1

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

African (AFR) AF: 0.936 AC: 19889 AN: 21240

American (AMR) AF: 0.891 AC: 19930 AN: 22376

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 14103 AN: 16416

East Asian (EAS) AF: 0.949 AC: 30879 AN: 32534

South Asian (SAS) AF: 0.761 AC: 40312 AN: 52984

European-Finnish (FIN) AF: 0.869 AC: 29199 AN: 33608

Middle Eastern (MID) AF: 0.813 AC: 2434 AN: 2994

European-Non Finnish (NFE) AF: 0.870 AC: 651069 AN: 748372

Other (OTH) AF: 0.874 AC: 37032 AN: 42354

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

African (AFR) AF: 0.930 AC: 38635 AN: 41522

American (AMR) AF: 0.897 AC: 13711 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4877 AN: 5186

South Asian (SAS) AF: 0.751 AC: 3622 AN: 4822

European-Finnish (FIN) AF: 0.877 AC: 9274 AN: 10570

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59202 AN: 68002

Other (OTH) AF: 0.869 AC: 1832 AN: 2108

Alfa AF: 0.876 Hom.: 73795

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
PhyloP100		0.12
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: rs3034; hg19: chr10-30749895;