3-27312225-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394966.1(NEK10):​c.490-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 985,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>A		intron	N/A	NP_001381895.1	A0A8I5KTB8
	NEK10	NM_001394970.1		c.490-48G>A		intron	N/A	NP_001381899.1	Q6ZWH5-1
	NEK10	NM_152534.6		c.490-48G>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.490-48G>A		intron	N/A	ENSP00000509472.1	A0A8I5KTB8
	NEK10	ENST00000429845.6	TSL:5	c.490-48G>A		intron	N/A	ENSP00000395849.2	Q6ZWH5-1
	NEK10	ENST00000936071.1		c.490-48G>A		intron	N/A	ENSP00000606130.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 985778 Hom.: 0 Cov.: 12 AF XY: 0.00000200 AC XY: 1 AN XY: 500152

African (AFR) AF: 0.00 AC: 0 AN: 22668

American (AMR) AF: 0.00 AC: 0 AN: 28190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20486

East Asian (EAS) AF: 0.00 AC: 0 AN: 34196

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 63062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 720640

Other (OTH) AF: 0.00 AC: 0 AN: 43722

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.014
DANN	Benign	0.81
PhyloP100		-0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;