rs56302559

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003954.5(MAP3K14):c.2290A>G(p.Thr764Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,606,984 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T764I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 6 hom. )

Consequence

MAP3K14
NM_003954.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.701

Publications

5 publications found

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:

MAP3K14-AS1 (HGNC:44359): (MAP3K14 antisense RNA 1)

MAP3K14-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003954.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007188499).

BP6

Variant 17-45267442-T-C is Benign according to our data. Variant chr17-45267442-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 478059.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K14	NM_003954.5	MANE Select	c.2290A>G	p.Thr764Ala	missense	Exon 12 of 16	NP_003945.2	Q99558
MAP3K14-AS1	NR_024434.2		n.295+114T>C		intron	N/A
MAP3K14-AS1	NR_024435.2		n.749+114T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K14	ENST00000344686.8	TSL:1 MANE Select	c.2290A>G	p.Thr764Ala	missense	Exon 12 of 16	ENSP00000478552.1	Q99558
MAP3K14	ENST00000376926.8	TSL:1	c.2290A>G	p.Thr764Ala	missense	Exon 11 of 15	ENSP00000482657.1	Q99558
MAP3K14-AS1	ENST00000585351.2	TSL:1	n.638+114T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00188

AC:

442

AN:

235416

AF XY:

0.00177

show subpopulations

Gnomad AFR exome

AF:

0.000856

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00122

GnomAD4 exome

AF:

0.00299

AC:

4352

AN:

1454650

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2037

AN XY:

723094

show subpopulations

African (AFR)

AF:

0.000630

AC:

AN:

33344

American (AMR)

AF:

0.000485

AC:

AN:

43308

Ashkenazi Jewish (ASJ)

AF:

0.000155

AC:

AN:

25886

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.000106

AC:

AN:

85120

European-Finnish (FIN)

AF:

0.000905

AC:

AN:

53050

Middle Eastern (MID)

AF:

0.000354

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00375

AC:

4153

AN:

1108694

Other (OTH)

AF:

0.00156

AC:

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

254

507

761

1014

1268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152334

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41582

American (AMR)

AF:

0.00144

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00178

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

NIK deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.29

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0072

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

PhyloP100

0.70

PrimateAI

Benign

0.35

REVEL

Benign

0.052

Sift4G

Benign

0.45

Varity_R

0.043

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over