rs367938510

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003954.5(MAP3K14):c.1546G>A(p.Val516Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,609,690 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

MAP3K14
NM_003954.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.47

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015393168).

BP6

Variant 17-45274129-C-T is Benign according to our data. Variant chr17-45274129-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 544325.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-45274129-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5 link	c.1546G>A	p.Val516Ile	missense_variant	Exon 8 of 16	ENST00000344686.8	NP_003945.2	Q99558Q68D39
MAP3K14	XM_047436997.1 link	c.1546G>A	p.Val516Ile	missense_variant	Exon 8 of 15		XP_047292953.1
MAP3K14	XM_047436998.1 link	c.1546G>A	p.Val516Ile	missense_variant	Exon 9 of 16		XP_047292954.1
MAP3K14	XM_011525441.3 link	c.1546G>A	p.Val516Ile	missense_variant	Exon 9 of 17		XP_011523743.1	Q99558

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8 link	c.1546G>A	p.Val516Ile	missense_variant	Exon 8 of 16	1	NM_003954.5	ENSP00000478552.1		Q99558

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00108

AC:

259

AN:

239846

Hom.:

AF XY:

0.00118

AC XY:

153

AN XY:

130120

show subpopulations

Gnomad AFR exome

AF:

0.000339

Gnomad AMR exome

AF:

0.000623

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00260

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.000686

GnomAD4 exome

AF:

0.00172

AC:

2508

AN:

1457380

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1290

AN XY:

724486

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000792

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00291

Gnomad4 FIN exome

AF:

0.000207

Gnomad4 NFE exome

AF:

0.00190

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152310

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000761

AC:

ESP6500EA

AF:

0.000844

AC:

ExAC

AF:

0.00110

AC:

133

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

NIK deficiency

Benign:1

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.80

.;T;.

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.41

N;N;N

PrimateAI

Benign

0.40

REVEL

Benign

0.23

Sift4G

Benign

0.69

.;T;T

Polyphen

0.022

B;B;B

Vest4

0.20, 0.20

MVP

0.27

ClinPred

0.058

GERP RS

3.0

Varity_R

0.032

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over