3-131133886-A-G

Variant names:

• chr3-131133886-A-G
• NM_024800.5:c.577A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024800.5(NEK11):​c.577A>G​(p.Thr193Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: 4.26

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3985355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK11	NM_024800.5	c.577A>G	p.Thr193Ala	missense_variant	Exon 7 of 18	ENST00000383366.9	NP_079076.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK11	ENST00000383366.9	c.577A>G	p.Thr193Ala	missense_variant	Exon 7 of 18	1	NM_024800.5	ENSP00000372857.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.577A>G (p.T193A) alteration is located in exon 7 (coding exon 5) of the NEK11 gene. This alteration results from a A to G substitution at nucleotide position 577, causing the threonine (T) at amino acid position 193 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.;.;T;.;.;T
Eigen	Benign	0.0011
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T;T;.;.;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.42	.;N;N;N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.5	D;D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.037	D;T;T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T;T
Polyphen		0.86	P;P;P;P;P;P;P
Vest4		0.31
MutPred		0.63		Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);Gain of glycosylation at Y198 (P = 0.0092);
MVP		0.74
MPC		0.19
ClinPred		0.88	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-130852730;