rs55740287

Variant names:

• chr17-45290614-G-A
• rs55740287
• NM_003954.5:c.132C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-45290614-G-A
• chr17-45290614-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.559
• Publications: 5 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 Gene-Disease associations (from GenCC):

• NIK deficiency

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

ACMG classification

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

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.132C>T	p.Ala44Ala	synonymous	Exon 2 of 16	NP_003945.2	Q99558

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K14	ENST00000344686.8	TSL:1 MANE Select	c.132C>T	p.Ala44Ala	synonymous	Exon 2 of 16	ENSP00000478552.1	Q99558
	MAP3K14	ENST00000376926.8	TSL:1	c.132C>T	p.Ala44Ala	synonymous	Exon 1 of 15	ENSP00000482657.1	Q99558
	MAP3K14	ENST00000970424.1		c.132C>T	p.Ala44Ala	synonymous	Exon 2 of 16	ENSP00000640483.1

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

GnomAD2 exomes AF: 0.00454 AC: 1133 AN: 249304 AF XY: 0.00446

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

African (AFR) AF: 0.000717 AC: 24 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: 1 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: 87 AN: 5768

European-Non Finnish (NFE) AF: 0.00418 AC: 4649 AN: 1111870

Other (OTH) AF: 0.00508 AC: 307 AN: 60374

GnomAD4 genome AF: 0.00393 AC: 597 AN: 151966 Hom.: 5 Cov.: 31 AF XY: 0.00416 AC XY: 309 AN XY: 74258

African (AFR) AF: 0.000724 AC: 30 AN: 41450

American (AMR) AF: 0.00347 AC: 53 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4812

European-Finnish (FIN) AF: 0.00900 AC: 95 AN: 10550

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00502 AC: 341 AN: 67994

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00496 Hom.: 1

Bravo AF: 0.00337

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	NIK deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.56
PromoterAI		-0.045	Neutral

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: rs55740287; hg19: chr17-43367980;