rs1357245

Variant names:

• chr3-27145111-C-T
• rs1357245
• NM_001394966.1:c.2870-3529G>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.2870-3529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 150,984 control chromosomes in the GnomAD database, including 12,040 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 0.36 (12040 hom., cov: 31)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 8 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: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	NM_001394966.1	MANE Select	c.2870-3529G>A		intron	N/A	NP_001381895.1
	NEK10	NM_001394970.1		c.3011-1637G>A		intron	N/A	NP_001381899.1
	NEK10	NM_152534.6		c.3011-1637G>A		intron	N/A	NP_689747.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK10	ENST00000691995.1	MANE Select	c.2870-3529G>A		intron	N/A	ENSP00000509472.1
	NEK10	ENST00000383771.8	TSL:1	c.947-3529G>A		intron	N/A	ENSP00000373281.4
	NEK10	ENST00000429845.6	TSL:5	c.3011-1637G>A		intron	N/A	ENSP00000395849.2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54639 AN: 150866 Hom.: 12040 Cov.: 31

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.362 AC: 54651 AN: 150984 Hom.: 12040 Cov.: 31 AF XY: 0.367 AC XY: 27010 AN XY: 73666

African (AFR) AF: 0.0965 AC: 3970 AN: 41136

American (AMR) AF: 0.422 AC: 6353 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1461 AN: 3464

East Asian (EAS) AF: 0.752 AC: 3872 AN: 5152

South Asian (SAS) AF: 0.446 AC: 2117 AN: 4750

European-Finnish (FIN) AF: 0.463 AC: 4785 AN: 10336

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30761 AN: 67794

Other (OTH) AF: 0.378 AC: 792 AN: 2094

Alfa AF: 0.432 Hom.: 6864

Bravo AF: 0.346

Asia WGS AF: 0.527 AC: 1826 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.71
PhyloP100		-1.3
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: rs1357245; hg19: chr3-27186602;