Variant chr3-27284960-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001394966.1(NEK10):c.1791T>C(p.Asn597Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,586,054 control chromosomes in the GnomAD database, including 54,845 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4675 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50170 hom. )

Consequence

NEK10
NM_001394966.1 splice_region, synonymous

Scores

Splicing: ADA: 0.4034

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.20

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:

NEK10 (HGNC:):

NEK10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 3-27284960-A-G is Benign according to our data. Variant chr3-27284960-A-G is described in ClinVar as [Benign]. Clinvar id is 1325895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK10	NM_001394966.1 linkuse as main transcript	c.1791T>C	p.Asn597Asn	splice_region_variant, synonymous_variant	21/36	ENST00000691995.1	NP_001381895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK10	ENST00000691995.1 linkuse as main transcript	c.1791T>C	p.Asn597Asn	splice_region_variant, synonymous_variant	21/36		NM_001394966.1	ENSP00000509472.1		A0A8I5KTB8

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36165

AN:

152040

Hom.:

4675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.0951

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.276

AC:

63652

AN:

230822

Hom.:

9364

AF XY:

0.280

AC XY:

35078

AN XY:

125424

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.258

AC:

369673

AN:

1433896

Hom.:

50170

Cov.:

AF XY:

0.261

AC XY:

186173

AN XY:

713844

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.0911

Gnomad4 SAS exome

AF:

0.304

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.238

AC:

36174

AN:

152158

Hom.:

4675

Cov.:

AF XY:

0.242

AC XY:

18024

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.0954

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.271

Hom.:

12489

Bravo

AF:

0.236

Asia WGS

AF:

0.186

AC:

649

AN:

3478

EpiCase

AF:

0.292

EpiControl

AF:

0.294

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Ciliary dyskinesia, primary, 44

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.40

dbscSNV1_RF

Benign

0.16

SpliceAI score (max)

0.040

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