Variant 3-27291542-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001394966.1(NEK10):c.1418A>C(p.His473Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000096 in 1,457,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NEK10
NM_001394966.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

Variant links:

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]

NEK10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK10	NM_001394966.1 linkuse as main transcript	c.1418A>C	p.His473Pro	missense_variant	17/36	ENST00000691995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK10	ENST00000691995.1 linkuse as main transcript	c.1418A>C	p.His473Pro	missense_variant	17/36		NM_001394966.1	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248658

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1457798

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725490

show subpopulations

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:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.1418A>C (p.H473P) alteration is located in exon 18 (coding exon 16) of the NEK10 gene. This alteration results from a A to C substitution at nucleotide position 1418, causing the histidine (H) at amino acid position 473 to be replaced by a proline (P). 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

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.25

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.51

Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);

MVP

0.91

MPC

0.65

ClinPred

0.98

GERP RS

5.5

Varity_R

0.46

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over