NM_001199397.3:c.3848-198C>T

Variant names:

• chr4-169394721-G-A
• rs13131146
• NM_001199397.3:c.3848-198C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001199397.3(NEK1):​c.3848-198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,950 control chromosomes in the GnomAD database, including 10,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10174 hom., cov: 33)
• Consequence: NEK1 NM_001199397.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.608
• 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-169394721-G-A is Benign according to our data. Variant chr4-169394721-G-A is described in ClinVar as Benign. ClinVar VariationId is 667932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

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.3848-198C>T		intron	N/A	NP_001186326.1	Q96PY6-3
	NEK1	NM_001374418.1		c.3848-198C>T		intron	N/A	NP_001361347.1	Q96PY6-3
	NEK1	NM_001374419.1		c.3764-198C>T		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.3848-198C>T		intron	N/A	ENSP00000424757.2	Q96PY6-3
	NEK1	ENST00000439128.6	TSL:1	c.3764-198C>T		intron	N/A	ENSP00000408020.2	Q96PY6-1
	NEK1	ENST00000511633.5	TSL:1	c.3716-198C>T		intron	N/A	ENSP00000423332.1	Q96PY6-6

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54287 AN: 151832 Hom.: 10151 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.358 AC: 54353 AN: 151950 Hom.: 10174 Cov.: 33 AF XY: 0.357 AC XY: 26521 AN XY: 74284

African (AFR) AF: 0.441 AC: 18243 AN: 41412

American (AMR) AF: 0.306 AC: 4677 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3468

East Asian (EAS) AF: 0.0678 AC: 351 AN: 5178

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3075 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23652 AN: 67908

Other (OTH) AF: 0.332 AC: 701 AN: 2112

Alfa AF: 0.356 Hom.: 3747

Bravo AF: 0.354

Asia WGS AF: 0.287 AC: 999 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.17
PhyloP100		-0.61
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: rs13131146; hg19: chr4-170315872;