rs189186475

Variant names:

• chr4-169562196-C-A
• NM_001199397.3:c.1021G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-169562196-C-A
• chr4-169562196-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001199397.3(NEK1):​c.1021G>T​(p.Ala341Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NEK1 NM_001199397.3 missense, splice_region
• Scores: Splicing: ADA: 0.9934
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK1	NM_001199397.3	c.1021G>T	p.Ala341Ser	missense_variant, splice_region_variant	Exon 13 of 36	ENST00000507142.6	NP_001186326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK1	ENST00000507142.6	c.1021G>T	p.Ala341Ser	missense_variant, splice_region_variant	Exon 13 of 36	1	NM_001199397.3	ENSP00000424757.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376346 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 678760

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Uncertain	0.051	T;T;T;D;D
Polyphen		0.82	P;.;D;P;P
Vest4		0.23
MutPred		0.20		Gain of phosphorylation at A341 (P = 0.0431);Gain of phosphorylation at A341 (P = 0.0431);Gain of phosphorylation at A341 (P = 0.0431);Gain of phosphorylation at A341 (P = 0.0431);Gain of phosphorylation at A341 (P = 0.0431);
MVP		0.67
MPC		0.26
ClinPred		0.93	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-170483347;