chr4-169561895-AAATA-AAAT

Variant names:

• chr4-169561897-AT-AT
• NM_001199397.3:c.

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001199397.3(NEK1):​c. variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NEK1 NM_001199397.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 0 publications found

Genes affected

NEK1 (HGNC:7744): (NIMA related kinase 1) The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

NEK1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis, susceptibility to, 24

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• short-rib thoracic dysplasia 6 with or without polydactyly

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type II

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199397.3. 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
	NEK1	NM_001199397.3	MANE Select	c.		splice_region intron	N/A	NP_001186326.1	Q96PY6-3
	NEK1	NM_001374418.1		c.		splice_region intron	N/A	NP_001361347.1	Q96PY6-3
	NEK1	NM_001374419.1		c.		splice_region intron	N/A	NP_001361348.1	Q96PY6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK1	ENST00000507142.6	TSL:1 MANE Select	c.		splice_region intron	N/A	ENSP00000424757.2	Q96PY6-3
	NEK1	ENST00000439128.6	TSL:1	c.		splice_region intron	N/A	ENSP00000408020.2	Q96PY6-1
	NEK1	ENST00000511633.5	TSL:1	c.		splice_region intron	N/A	ENSP00000423332.1	Q96PY6-6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-170483048;