4-169393959-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001199397.3(NEK1):c.*551A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 152,288 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEK1 NM_001199397.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.665

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 4-169393959-T-A is Benign according to our data. Variant chr4-169393959-T-A is described in ClinVar as [Benign]. Clinvar id is 899464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00361 (550/152288) while in subpopulation AMR AF= 0.026 (398/15292). AF 95% confidence interval is 0.0239. There are 11 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK1	NM_001199397.3	c.*551A>T		3_prime_UTR_variant	36/36	ENST00000507142.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK1	ENST00000507142.6	c.*551A>T		3_prime_UTR_variant	36/36	1	NM_001199397.3	A2

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 553 AN: 152170 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00526

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00361 AC: 550 AN: 152288 Hom.: 11 Cov.: 33 AF XY: 0.00389 AC XY: 290 AN XY: 74470

Gnomad4 AFR AF: 0.00205

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00216

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00244 Hom.: 2

Bravo AF: 0.00642

Asia WGS AF: 0.00289 AC: 10 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Short-rib thoracic dysplasia 6 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	8.5
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs181225797; hg19: chr4-170315110;