3-131080442-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024800.5(NEK11):c.190T>A(p.Ser64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NEK11 NM_024800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20054254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK11	NM_024800.5	c.190T>A	p.Ser64Thr	missense_variant	4/18	ENST00000383366.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK11	ENST00000383366.9	c.190T>A	p.Ser64Thr	missense_variant	4/18	1	NM_024800.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450142 Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 720954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000361

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

May 27, 2022

The c.190T>A (p.S64T) alteration is located in exon 4 (coding exon 2) of the NEK11 gene. This alteration results from a T to A substitution at nucleotide position 190, causing the serine (S) at amino acid position 64 to be replaced by a threonine (T). 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	0.085
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.;.;T;.;.;T
Eigen	Benign	-0.0063
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D;D;.;.;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.049	D;T;T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T;T;T
Polyphen		0.87	P;P;B;P;P;B;P
Vest4		0.093
MutPred		0.42		Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);Gain of glycosylation at S64 (P = 0.0452);
MVP		0.69
MPC		0.16
ClinPred		0.72	D
GERP RS		4.6
Varity_R		0.27
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr3-130799286;