chr3-131080550-G-C

Position:

• chr3-131080550-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024800.5(NEK11):​c.298G>C​(p.Glu100Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK11 NM_024800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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]

NEK11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37632042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK11	NM_024800.5	c.298G>C	p.Glu100Gln	missense_variant	4/18	ENST00000383366.9	NP_079076.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9	c.298G>C	p.Glu100Gln	missense_variant	4/18	1	NM_024800.5	ENSP00000372857.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.298G>C (p.E100Q) alteration is located in exon 4 (coding exon 2) of the NEK11 gene. This alteration results from a G to C substitution at nucleotide position 298, causing the glutamic acid (E) at amino acid position 100 to be replaced by a glutamine (Q). 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	0.17
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;.;.;T;.;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;.;.;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.82	.;L;L;L;L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.017	D;D;D;D;D;D;D
Sift4G	Benign	0.096	T;T;D;T;D;D;T
Polyphen		0.99	D;D;D;D;D;D;D
Vest4		0.33
MutPred		0.48		Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);
MVP		0.70
MPC		0.23
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.36
gMVP		0.50

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

Other links and lift over

dbSNP: rs1399040404; hg19: chr3-130799394;