3-131152509-C-T

Variant names:

• chr3-131152509-C-T
• rs1040285554
• NM_024800.5:c.769C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024800.5(NEK11):​c.769C>T​(p.Pro257Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 2.70
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08716282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024800.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK11	NM_024800.5	MANE Select	c.769C>T	p.Pro257Ser	missense	Exon 8 of 18	NP_079076.3
	NEK11	NM_001321221.2		c.895C>T	p.Pro299Ser	missense	Exon 9 of 19	NP_001308150.1
	NEK11	NM_001353022.2		c.895C>T	p.Pro299Ser	missense	Exon 9 of 19	NP_001339951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK11	ENST00000383366.9	TSL:1 MANE Select	c.769C>T	p.Pro257Ser	missense	Exon 8 of 18	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.769C>T	p.Pro257Ser	missense	Exon 7 of 16	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000507910.5	TSL:1	c.769C>T	p.Pro257Ser	missense	Exon 7 of 14	ENSP00000426662.1	Q8NG66-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.15
DEOGEN2	Benign	0.00072	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.098
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.14	B
Vest4		0.36
MutPred		0.55		Loss of glycosylation at P257 (P = 0.043)
MVP		0.35
MPC		0.033
ClinPred		0.34	T
GERP RS		4.9
Varity_R		0.070
gMVP		0.28
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1040285554; hg19: chr3-130871353;