Variant rs113278485 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_003954.5(MAP3K14):c.880A>G(p.Lys294Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAP3K14
NM_003954.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Variant links:

Genes affected

MAP3K14 (HGNC:6853): (mitogen-activated protein kinase kinase kinase 14) This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008]

MAP3K14 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAP3K14. . Trascript score misZ 4.5031 (greater than threshold 3.09). GenCC has associacion of gene with NIK deficiency.

BP4

Computational evidence support a benign effect (MetaRNN=0.047301173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAP3K14	NM_003954.5 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	5/16	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	5/15		XP_047292953.1
MAP3K14	XM_047436998.1 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	6/16		XP_047292954.1
MAP3K14	XM_011525441.3 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	6/17		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAP3K14	ENST00000344686.8 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	5/16	1	NM_003954.5	ENSP00000478552	P1
MAP3K14	ENST00000376926.8 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	4/15	1		ENSP00000482657	P1
MAP3K14	ENST00000617331.3 linkuse as main transcript	c.880A>G	p.Lys294Glu	missense_variant	6/17	5		ENSP00000480974	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240214

Hom.:

AF XY:

0.00000768

AC XY:

AN XY:

130292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000916

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.22

.;T;.

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.29

REVEL

Benign

0.065

Sift4G

Benign

0.40

.;T;T

Polyphen

0.0080

B;B;B

Vest4

0.14, 0.13

MutPred

0.28

Loss of ubiquitination at K294 (P = 0.0014);Loss of ubiquitination at K294 (P = 0.0014);Loss of ubiquitination at K294 (P = 0.0014);

MVP

0.10

ClinPred

0.050

GERP RS

-1.4

Varity_R

0.075

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over