chr3-27290667-C-T

Variant names:

• chr3-27290667-C-T
• rs2042933089
• NM_001394966.1:c.1693G>A

Variant summary

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

The NM_001394966.1(NEK10):​c.1693G>A​(p.Asp565Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NEK10 NM_001394966.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

Genes affected

NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

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=0.35454386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK10	NM_001394966.1	c.1693G>A	p.Asp565Asn	missense_variant	Exon 19 of 36	ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1	c.1693G>A	p.Asp565Asn	missense_variant	Exon 19 of 36		NM_001394966.1	ENSP00000509472.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456202 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 724658

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1693G>A (p.D565N) alteration is located in exon 20 (coding exon 18) of the NEK10 gene. This alteration results from a G to A substitution at nucleotide position 1693, causing the aspartic acid (D) at amino acid position 565 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0032	T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.10
Sift	Benign	0.067	.;T
Sift4G	Uncertain	0.049	D;D
Polyphen		0.84	P;.
Vest4		0.42
MutPred		0.68		Gain of glycosylation at S567 (P = 0.0073);Gain of glycosylation at S567 (P = 0.0073);
MVP		0.73
MPC		0.40
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.49
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2042933089; hg19: chr3-27332158;