3-131349675-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024800.5(NEK11):​c.1837C>T​(p.Pro613Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NEK11
NM_024800.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21
Variant links:
Genes affected
NEK11 (HGNC:18593): (NIMA related kinase 11) This gene encodes a member of the never in mitosis gene A family of kinases. The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. The encoded protein appears to play roles in DNA replication and response to genotoxic stress. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2009]
NUDT16-DT (HGNC:27947): (NUDT16 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02917859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK11NM_024800.5 linkc.1837C>T p.Pro613Ser missense_variant Exon 18 of 18 ENST00000383366.9 NP_079076.3 Q8NG66-1B4DM56

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK11ENST00000383366.9 linkc.1837C>T p.Pro613Ser missense_variant Exon 18 of 18 1 NM_024800.5 ENSP00000372857.4 Q8NG66-1

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251162
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000746
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000395
Hom.:
0
Bravo
AF:
0.000336
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1837C>T (p.P613S) alteration is located in exon 18 (coding exon 16) of the NEK11 gene. This alteration results from a C to T substitution at nucleotide position 1837, causing the proline (P) at amino acid position 613 to be replaced by a serine (S). 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
0.098
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
T;T;T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.74
T;.;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.029
T;T;T
MetaSVM
Benign
-0.85
T
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.088
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.48
T;T;T
Polyphen
0.95
P;P;P
Vest4
0.13
MVP
0.75
MPC
0.031
ClinPred
0.24
T
GERP RS
5.7
Varity_R
0.090
gMVP
0.12

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: rs144885382; hg19: chr3-131068519; API