3-27302153-C-T

Variant names:

• chr3-27302153-C-T
• rs653465
• NM_001394966.1:c.1029-318G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394966.1(NEK10):​c.1029-318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,066 control chromosomes in the GnomAD database, including 33,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33061 hom., cov: 32)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 44

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394966.1. 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
	NEK10	NM_001394966.1	MANE Select	c.1029-318G>A		intron	N/A	NP_001381895.1	A0A8I5KTB8
	NEK10	NM_001394970.1		c.1029-318G>A		intron	N/A	NP_001381899.1	Q6ZWH5-1
	NEK10	NM_152534.6		c.1029-318G>A		intron	N/A	NP_689747.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	ENST00000691995.1	MANE Select	c.1029-318G>A		intron	N/A	ENSP00000509472.1	A0A8I5KTB8
	NEK10	ENST00000429845.6	TSL:5	c.1029-318G>A		intron	N/A	ENSP00000395849.2	Q6ZWH5-1
	NEK10	ENST00000936071.1		c.1029-318G>A		intron	N/A	ENSP00000606130.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96618 AN: 151948 Hom.: 33003 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.636 AC: 96736 AN: 152066 Hom.: 33061 Cov.: 32 AF XY: 0.632 AC XY: 46963 AN XY: 74332

African (AFR) AF: 0.906 AC: 37629 AN: 41554

American (AMR) AF: 0.624 AC: 9524 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1979 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1353 AN: 5166

South Asian (SAS) AF: 0.500 AC: 2412 AN: 4826

European-Finnish (FIN) AF: 0.535 AC: 5633 AN: 10534

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36201 AN: 67934

Other (OTH) AF: 0.621 AC: 1311 AN: 2112

Alfa AF: 0.550 Hom.: 40046

Bravo AF: 0.657

Asia WGS AF: 0.463 AC: 1611 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.30
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs653465; hg19: chr3-27343644;