rs55740287

chr17-45290614-G-Achr17-45290614-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.559

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]

ACMG classification

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 GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K14	NM_003954.5	c.132C>T	p.Ala44=	synonymous_variant	2/16	ENST00000344686.8
MAP3K14	XM_047436997.1	c.132C>T	p.Ala44=	synonymous_variant	2/15
MAP3K14	XM_047436998.1	c.132C>T	p.Ala44=	synonymous_variant	3/16
MAP3K14	XM_011525441.3	c.132C>T	p.Ala44=	synonymous_variant	3/17

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00393 AC: 597 AN: 151848 Hom.: 5 Cov.: 31

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.: 5 AF XY: 0.00446 AC XY: 603 AN XY: 135252

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.: 24 Cov.: 31 AF XY: 0.00438 AC XY: 3185 AN XY: 727138

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.: 5 Cov.: 31 AF XY: 0.00416 AC XY: 309 AN XY: 74258

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.: 1

Bravo AF: 0.00337

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

NIK deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs55740287; hg19: chr17-43367980;