3-131133866-G-T

Variant names:

• chr3-131133866-G-T
• NM_024800.5:c.557G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024800.5(NEK11):​c.557G>T​(p.Cys186Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 8.59

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK11	NM_024800.5	c.557G>T	p.Cys186Phe	missense_variant	Exon 7 of 18	ENST00000383366.9	NP_079076.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9	c.557G>T	p.Cys186Phe	missense_variant	Exon 7 of 18	1	NM_024800.5	ENSP00000372857.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.557G>T (p.C186F) alteration is located in exon 7 (coding exon 5) of the NEK11 gene. This alteration results from a G to T substitution at nucleotide position 557, causing the cysteine (C) at amino acid position 186 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;.;.;T;.;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;.;.;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.49	.;N;N;N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.12	T;T;T;T;T;T;T
Sift4G	Uncertain	0.028	D;T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;D;D
Vest4		0.75
MutPred		0.38		Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);Gain of glycosylation at T191 (P = 0.0318);
MVP		0.70
MPC		0.19
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.61
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr3-130852710;