NM_024800.5:c.1463A>T

Variant names:

• chr3-131228591-A-T
• rs3738000
• NM_024800.5:c.1463A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024800.5(NEK11):​c.1463A>T​(p.Glu488Val) variant causes a missense change. The variant allele was found at a frequency of 0.674 in 1,612,750 control chromosomes in the GnomAD database, including 376,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. E488A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.56 (27155 hom., cov: 32)
  • Exomes 𝑓: 0.69 (349069 hom.)
• Consequence: NEK11 NM_024800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10
• Publications: 38 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

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.1463A>T	p.Glu488Val	missense	Exon 15 of 18	NP_079076.3
	NEK11	NM_001321221.2		c.1589A>T	p.Glu530Val	missense	Exon 16 of 19	NP_001308150.1
	NEK11	NM_001353022.2		c.1589A>T	p.Glu530Val	missense	Exon 16 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.1463A>T	p.Glu488Val	missense	Exon 15 of 18	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.1463A>T	p.Glu488Val	missense	Exon 14 of 16	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000972131.1		c.1643A>T	p.Glu548Val	missense	Exon 15 of 18	ENSP00000642190.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85351 AN: 151890 Hom.: 27156 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.584

GnomAD2 exomes AF: 0.648 AC: 162528 AN: 250702 AF XY: 0.663

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.726

Gnomad EAS exome AF: 0.387

Gnomad FIN exome AF: 0.696

Gnomad NFE exome AF: 0.712

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.685 AC: 1001204 AN: 1460740 Hom.: 349069 Cov.: 38 AF XY: 0.689 AC XY: 501019 AN XY: 726680

African (AFR) AF: 0.240 AC: 8039 AN: 33442

American (AMR) AF: 0.630 AC: 28126 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 19023 AN: 26122

East Asian (EAS) AF: 0.438 AC: 17371 AN: 39672

South Asian (SAS) AF: 0.743 AC: 64035 AN: 86174

European-Finnish (FIN) AF: 0.702 AC: 37484 AN: 53378

Middle Eastern (MID) AF: 0.740 AC: 4263 AN: 5760

European-Non Finnish (NFE) AF: 0.705 AC: 783185 AN: 1111164

Other (OTH) AF: 0.657 AC: 39678 AN: 60350

GnomAD4 genome AF: 0.562 AC: 85358 AN: 152010 Hom.: 27155 Cov.: 32 AF XY: 0.563 AC XY: 41823 AN XY: 74300

African (AFR) AF: 0.252 AC: 10454 AN: 41460

American (AMR) AF: 0.615 AC: 9376 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2503 AN: 3466

East Asian (EAS) AF: 0.400 AC: 2072 AN: 5180

South Asian (SAS) AF: 0.727 AC: 3496 AN: 4808

European-Finnish (FIN) AF: 0.688 AC: 7261 AN: 10550

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48165 AN: 67986

Other (OTH) AF: 0.582 AC: 1225 AN: 2104

Alfa AF: 0.678 Hom.: 26984

Bravo AF: 0.538

TwinsUK AF: 0.704 AC: 2612

ALSPAC AF: 0.699 AC: 2695

ESP6500AA AF: 0.260 AC: 1145

ESP6500EA AF: 0.708 AC: 6092

ExAC AF: 0.645 AC: 78331

Asia WGS AF: 0.554 AC: 1928 AN: 3478

EpiCase AF: 0.714

EpiControl AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0000080	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.39
Sift	Benign	0.056	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.24
ClinPred		0.024	T
GERP RS		5.7
Varity_R		0.15
gMVP		0.42
Mutation Taster		=87/13	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3738000; hg19: chr3-130947435; COSMIC: COSV67279869;