9-124321566-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014397.6(NEK6):​c.402C>G​(p.Ile134Met) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

NEK6
NM_014397.6 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10
Variant links:
Genes affected
NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK6NM_014397.6 linkc.402C>G p.Ile134Met missense_variant Exon 5 of 10 ENST00000320246.10 NP_055212.2 Q9HC98-1A0A024R8A6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK6ENST00000320246.10 linkc.402C>G p.Ile134Met missense_variant Exon 5 of 10 1 NM_014397.6 ENSP00000319734.5 Q9HC98-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.504C>G (p.I168M) alteration is located in exon 6 (coding exon 5) of the NEK6 gene. This alteration results from a C to G substitution at nucleotide position 504, causing the isoleucine (I) at amino acid position 168 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T;.;T;T;T;T;T;.;.;T;T;.;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;.;.;.;.;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.096
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.1
.;M;.;M;M;.;.;.;.;.;M;.;.;.;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0010
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;D;.;.;.;.;.;D;.;D;D;.
Vest4
0.83
MutPred
0.68
.;Gain of disorder (P = 0.0649);.;Gain of disorder (P = 0.0649);Gain of disorder (P = 0.0649);Gain of disorder (P = 0.0649);.;Gain of disorder (P = 0.0649);Gain of disorder (P = 0.0649);.;Gain of disorder (P = 0.0649);Gain of disorder (P = 0.0649);.;.;Gain of disorder (P = 0.0649);
MVP
0.86
MPC
2.2
ClinPred
0.94
D
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.66
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127083845; API