chr17-45286574-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_003954.5(MAP3K14):c.1009C>T(p.Leu337Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,611,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

MAP3K14
NM_003954.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.987

Publications

0 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 Gene-Disease associations (from GenCC):

NIK deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

MAP3K14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 17-45286574-G-A is Benign according to our data. Variant chr17-45286574-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 544335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.987 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 5 of 16	ENST00000344686.8	NP_003945.2	Q99558Q68D39
MAP3K14	XM_047436997.1 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 5 of 15		XP_047292953.1
MAP3K14	XM_047436998.1 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 6 of 16		XP_047292954.1
MAP3K14	XM_011525441.3 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 6 of 17		XP_011523743.1	Q99558

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAP3K14	ENST00000344686.8 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 5 of 16	1	NM_003954.5	ENSP00000478552.1	Q99558
MAP3K14	ENST00000376926.8 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 4 of 15	1		ENSP00000482657.1	Q99558
MAP3K14	ENST00000617331.3 link	c.1009C>T	p.Leu337Leu	synonymous_variant	Exon 6 of 17	5		ENSP00000480974.3	Q99558A0A087WXF1

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000476

AC:

116

AN:

243592

AF XY:

0.000423

show subpopulations

Gnomad AFR exome

AF:

0.000208

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00215

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000451

Gnomad OTH exome

AF:

0.000841

GnomAD4 exome

AF:

0.000663

AC:

967

AN:

1459036

Hom.:

Cov.:

AF XY:

0.000589

AC XY:

427

AN XY:

725496

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33420

American (AMR)

AF:

0.00147

AC:

AN:

44282

Ashkenazi Jewish (ASJ)

AF:

0.00181

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000708

AC:

786

AN:

1110928

Other (OTH)

AF:

0.00101

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000683

AC:

104

AN:

152312

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41552

American (AMR)

AF:

0.00222

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68032

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000769

Hom.:

Bravo

AF:

0.000854

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MAP3K14: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

NIK deficiency

Benign:1

Jan 12, 2025

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

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.9

(source)

DANN

Benign

0.74

PhyloP100

0.99

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over