chr3-27312225-C-A

Variant names:

• chr3-27312225-C-A
• rs552647
• NM_001394966.1:c.490-48G>T

Variant summary

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

The NM_001394966.1(NEK10):​c.490-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,134,696 control chromosomes in the GnomAD database, including 174,947 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 (33043 hom., cov: 32)
  • Exomes 𝑓: 0.53 (141904 hom.)
• Consequence: NEK10 NM_001394966.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 15 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=-0.89).
• 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.490-48G>T		intron	N/A	NP_001381895.1	A0A8I5KTB8
	NEK10	NM_001394970.1		c.490-48G>T		intron	N/A	NP_001381899.1	Q6ZWH5-1
	NEK10	NM_152534.6		c.490-48G>T		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.490-48G>T		intron	N/A	ENSP00000509472.1	A0A8I5KTB8
	NEK10	ENST00000429845.6	TSL:5	c.490-48G>T		intron	N/A	ENSP00000395849.2	Q6ZWH5-1
	NEK10	ENST00000936071.1		c.490-48G>T		intron	N/A	ENSP00000606130.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96552 AN: 151974 Hom.: 32987 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.551 AC: 94206 AN: 170998 AF XY: 0.543

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.527 AC: 517852 AN: 982604 Hom.: 141904 Cov.: 12 AF XY: 0.525 AC XY: 261732 AN XY: 498628

African (AFR) AF: 0.921 AC: 20862 AN: 22644

American (AMR) AF: 0.641 AC: 18034 AN: 28116

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 11487 AN: 20430

East Asian (EAS) AF: 0.254 AC: 8680 AN: 34152

South Asian (SAS) AF: 0.498 AC: 31319 AN: 62852

European-Finnish (FIN) AF: 0.516 AC: 24754 AN: 47996

Middle Eastern (MID) AF: 0.649 AC: 3052 AN: 4704

European-Non Finnish (NFE) AF: 0.523 AC: 375693 AN: 718092

Other (OTH) AF: 0.550 AC: 23971 AN: 43618

GnomAD4 genome AF: 0.636 AC: 96668 AN: 152092 Hom.: 33043 Cov.: 32 AF XY: 0.631 AC XY: 46929 AN XY: 74338

African (AFR) AF: 0.905 AC: 37606 AN: 41534

American (AMR) AF: 0.624 AC: 9530 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5156

South Asian (SAS) AF: 0.501 AC: 2412 AN: 4818

European-Finnish (FIN) AF: 0.535 AC: 5656 AN: 10570

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

European-Non Finnish (NFE) AF: 0.532 AC: 36176 AN: 67966

Other (OTH) AF: 0.620 AC: 1309 AN: 2112

Alfa AF: 0.563 Hom.: 97318

Bravo AF: 0.656

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.42
PhyloP100		-0.22
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: rs552647; hg19: chr3-27353716; COSMIC: COSV58283614;