rs1275224652

Variant names:

• chr17-45264758-G-A
• rs1275224652
• NM_003954.5:c.2722C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003954.5(MAP3K14):​c.2722C>T​(p.Pro908Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP3K14 NM_003954.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

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-AS1 (HGNC:44359): (MAP3K14 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35598397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K14	NM_003954.5	MANE Select	c.2722C>T	p.Pro908Ser	missense	Exon 16 of 16	NP_003945.2	Q99558
	MAP3K14-AS1	NR_024434.2		n.80-2355G>A		intron	N/A
	MAP3K14-AS1	NR_024435.2		n.265-1492G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K14	ENST00000344686.8	TSL:1 MANE Select	c.2722C>T	p.Pro908Ser	missense	Exon 16 of 16	ENSP00000478552.1	Q99558
	MAP3K14	ENST00000376926.8	TSL:1	c.2722C>T	p.Pro908Ser	missense	Exon 15 of 15	ENSP00000482657.1	Q99558
	MAP3K14-AS1	ENST00000585351.2	TSL:1	n.154-1492G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247138 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	NIK deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.4
PrimateAI	Benign	0.38	T
REVEL	Uncertain	0.32
Sift4G	Benign	0.21	T
Polyphen		0.92	P
Vest4		0.28
MutPred		0.26		Gain of sheet (P = 0.0221)
MVP		0.65
ClinPred		0.79	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.42

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

Other links and lift over

dbSNP: rs1275224652; hg19: chr17-43342125;