3-27284626-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001394966.1(NEK10):​c.1990G>C​(p.Gly664Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NEK10
NM_001394966.1 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41
Variant links:
Genes affected
NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK10NM_001394966.1 linkc.1990G>C p.Gly664Arg missense_variant Exon 22 of 36 ENST00000691995.1 NP_001381895.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK10ENST00000691995.1 linkc.1990G>C p.Gly664Arg missense_variant Exon 22 of 36 NM_001394966.1 ENSP00000509472.1 A0A8I5KTB8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1990G>C (p.G664R) alteration is located in exon 23 (coding exon 21) of the NEK10 gene. This alteration results from a G to C substitution at nucleotide position 1990, causing the glycine (G) at amino acid position 664 to be replaced by an arginine (R). 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
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.021
T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.030
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.93
L;L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-4.5
.;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.015
.;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.88
MutPred
0.69
Gain of ubiquitination at K666 (P = 0.0609);Gain of ubiquitination at K666 (P = 0.0609);
MVP
0.61
MPC
0.57
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.78
gMVP
0.62

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2042441123; hg19: chr3-27326117; API