3-131133881-C-G

Variant names:

• chr3-131133881-C-G
• rs145728410
• NM_024800.5:c.572C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024800.5(NEK11):​c.572C>G​(p.Thr191Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T191I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK11 NM_024800.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

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.572C>G	p.Thr191Ser	missense	Exon 7 of 18	NP_079076.3
	NEK11	NM_001321221.2		c.698C>G	p.Thr233Ser	missense	Exon 8 of 19	NP_001308150.1
	NEK11	NM_001353022.2		c.698C>G	p.Thr233Ser	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.572C>G	p.Thr191Ser	missense	Exon 7 of 18	ENSP00000372857.4	Q8NG66-1
	NEK11	ENST00000510688.5	TSL:1	c.572C>G	p.Thr191Ser	missense	Exon 6 of 16	ENSP00000423458.1	Q8NG66-4
	NEK11	ENST00000507910.5	TSL:1	c.572C>G	p.Thr191Ser	missense	Exon 6 of 14	ENSP00000426662.1	Q8NG66-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.45
Sift	Benign	0.080	T
Sift4G	Uncertain	0.060	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.83		Gain of glycosylation at T191 (P = 0.0318)
MVP		0.80
MPC		0.22
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.22
Mutation Taster		=67/33	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: rs145728410; hg19: chr3-130852725;