chr17-45290614-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003954.5(MAP3K14):c.132C>T(p.Ala44Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,613,678 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 24 hom. )

Consequence

MAP3K14
NM_003954.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.559

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 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 17-45290614-G-A is Benign according to our data. Variant chr17-45290614-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.559 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 2 of 16	ENST00000344686.8	NP_003945.2	Q99558Q68D39
MAP3K14	XM_047436997.1 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 2 of 15		XP_047292953.1
MAP3K14	XM_047436998.1 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 3 of 16		XP_047292954.1
MAP3K14	XM_011525441.3 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 3 of 17		XP_011523743.1	Q99558

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAP3K14	ENST00000344686.8 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 2 of 16	1	NM_003954.5	ENSP00000478552.1	Q99558
MAP3K14	ENST00000376926.8 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 1 of 15	1		ENSP00000482657.1	Q99558
MAP3K14	ENST00000617331.3 link	c.132C>T	p.Ala44Ala	synonymous_variant	Exon 3 of 17	5		ENSP00000480974.3	Q99558A0A087WXF1

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

597

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00900

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00454

AC:

1133

AN:

249304

AF XY:

0.00446

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00504

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00432

AC:

6320

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

3185

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00293

AC:

131

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

497

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00159

AC:

137

AN:

86258

European-Finnish (FIN)

AF:

0.00912

AC:

487

AN:

53402

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00418

AC:

4649

AN:

1111870

Other (OTH)

AF:

0.00508

AC:

307

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.00393

AC:

597

AN:

151966

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

309

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000724

AC:

AN:

41450

American (AMR)

AF:

0.00347

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00125

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00900

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00502

AC:

341

AN:

67994

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

128

160

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:

0.00496

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MAP3K14: BP4, BP7, BS2 -

Nov 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

NIK deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.73

CADD

Benign

2.1

(source)

DANN

Benign

0.56

PhyloP100

-0.56

PromoterAI

-0.045

Neutral

(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

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