Variant rs55740287 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003954.5(MAP3K14):c.132C>T(p.Ala44=) 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

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 -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 [Likely_benign]. Clinvar id is 478058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-45290614-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein
MAP3K14	NM_003954.5 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	2/16	ENST00000344686.8	NP_003945.2
MAP3K14	XM_047436997.1 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	2/15		XP_047292953.1
MAP3K14	XM_047436998.1 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	3/16		XP_047292954.1
MAP3K14	XM_011525441.3 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	3/17		XP_011523743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAP3K14	ENST00000344686.8 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	2/16	1	NM_003954.5	ENSP00000478552	P1
MAP3K14	ENST00000376926.8 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	1/15	1		ENSP00000482657	P1
MAP3K14	ENST00000617331.3 linkuse as main transcript	c.132C>T	p.Ala44=	synonymous_variant	3/17	5		ENSP00000480974	P1

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

GnomAD3 exomes

AF:

0.00454

AC:

1133

AN:

249304

Hom.:

AF XY:

0.00446

AC XY:

603

AN XY:

135252

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 SAS exome

AF:

0.00144

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

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.0190

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.00912

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00508

GnomAD4 genome

AF:

0.00393

AC:

597

AN:

151966

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

309

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.000724

Gnomad4 AMR

AF:

0.00347

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00900

Gnomad4 NFE

AF:

0.00502

Gnomad4 OTH

AF:

0.00378

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MAP3K14: BP4, BP7, BS2 -

NIK deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.1

DANN

Benign

0.56

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