NEK8 p.Met413Leu

Variant names:

• chr17-28738685-A-T
• NM_178170.3:c.1237A>T
• NEK8 p.Met413Leu

Your query was ambiguous. Multiple possible variants found:

• chr17-28738685-A-T
• chr17-28738685-A-C
• chr17-28738685-ATG-TTA
• chr17-28738685-ATG-CTT
• chr17-28738685-ATG-CTC
• chr17-28738685-ATG-CTA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178170.3(NEK8):​c.1237A>T​(p.Met413Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK8 NM_178170.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.93
• Publications: 0 publications found

Genes affected

NEK8 (HGNC:13387): (NIMA related kinase 8) This gene encodes a member of the serine/threionine protein kinase family related to NIMA (never in mitosis, gene A) of Aspergillus nidulans. The encoded protein may play a role in cell cycle progression from G2 to M phase. Mutations in the related mouse gene are associated with a disease phenotype that closely parallels the juvenile autosomal recessive form of polycystic kidney disease in humans. [provided by RefSeq, Jul 2008]

NEK8 Gene-Disease associations (from GenCC):

• renal-hepatic-pancreatic dysplasia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• nephronophthisis 9

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• polycystic kidney disease 8

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal-hepatic-pancreatic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000265073 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178170.3. 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
	NEK8	NM_178170.3	MANE Select	c.1237A>T	p.Met413Leu	missense	Exon 9 of 15	NP_835464.1	Q86SG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK8	ENST00000268766.11	TSL:1 MANE Select	c.1237A>T	p.Met413Leu	missense	Exon 9 of 15	ENSP00000268766.6	Q86SG6
	NEK8	ENST00000969681.1		c.1276A>T	p.Met426Leu	missense	Exon 9 of 15	ENSP00000639740.1
	NEK8	ENST00000903448.1		c.1105A>T	p.Met369Leu	missense	Exon 8 of 14	ENSP00000573507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	-0.77	N
PhyloP100		8.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.98	N
REVEL	Uncertain	0.63
Sift	Benign	0.12	T
Sift4G	Benign	0.68	T
Varity_R		0.35
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-27065703;