NM_024800.5:c.623G>C

Variant names:

• chr3-131133932-G-C
• NM_024800.5:c.623G>C

Variant summary

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

The NM_024800.5(NEK11):​c.623G>C​(p.Gly208Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 8.59
• 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.623G>C	p.Gly208Ala	missense	Exon 7 of 18	NP_079076.3
	NEK11	NM_001321221.2		c.749G>C	p.Gly250Ala	missense	Exon 8 of 19	NP_001308150.1
	NEK11	NM_001353022.2		c.749G>C	p.Gly250Ala	missense	Exon 8 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.623G>C	p.Gly208Ala	missense	Exon 7 of 18	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.623G>C	p.Gly208Ala	missense	Exon 6 of 16	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000507910.5	TSL:1	c.623G>C	p.Gly208Ala	missense	Exon 6 of 14	ENSP00000426662.1	Q8NG66-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458806 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725618

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110278

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

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	0.23
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.12	N
PhyloP100		8.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.36
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.62		Loss of ubiquitination at K205 (P = 0.0837)
MVP		0.77
MPC		0.23
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.46
gMVP		0.47
Mutation Taster		=49/51	disease causing

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

hg19: chr3-130852776;