3-131152509-C-G

Variant names:

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

Variant summary

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

The NM_024800.5(NEK11):​c.769C>G​(p.Pro257Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P257S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NEK11 NM_024800.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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>G	p.Pro257Ala	missense	Exon 8 of 18	NP_079076.3
	NEK11	NM_001321221.2		c.895C>G	p.Pro299Ala	missense	Exon 9 of 19	NP_001308150.1
	NEK11	NM_001353022.2		c.895C>G	p.Pro299Ala	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>G	p.Pro257Ala	missense	Exon 8 of 18	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.769C>G	p.Pro257Ala	missense	Exon 7 of 16	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000507910.5	TSL:1	c.769C>G	p.Pro257Ala	missense	Exon 7 of 14	ENSP00000426662.1	Q8NG66-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461104 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726812

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111594

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.047	D
Sift4G	Uncertain	0.029	D
Polyphen		0.86	P
Vest4		0.57
MutPred		0.58		Loss of glycosylation at P257 (P = 0.043)
MVP		0.59
MPC		0.11
ClinPred		0.87	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.21
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs1040285554; hg19: chr3-130871353;