3-52711071-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003157.6(NEK4):c.*706A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,464 control chromosomes in the GnomAD database, including 12,688 homozygotes. 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: 𝑓 0.39 (12649 hom., cov: 33)
  • Exomes 𝑓: 0.42 (39 hom.)
• Consequence: NEK4 NM_003157.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704

Genes affected

NEK4 (HGNC:11399): (NIMA related kinase 4) The protein encoded by this gene is a serine/threonine protein kinase required for normal entry into replicative senescence. The encoded protein also is involved in cell cycle arrest in response to double-stranded DNA damage. Finally, this protein plays a role in maintaining cilium integrity, and defects in this gene have been associated with ciliopathies. [provided by RefSeq, Jan 2017]

SPCS1 (HGNC:23401): (signal peptidase complex subunit 1) Predicted to enable peptidase activity and ribosome binding activity. Involved in viral protein processing and virion assembly. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK4	NM_003157.6	c.*706A>G		3_prime_UTR_variant	16/16	ENST00000233027.10
SPCS1	NM_014041.5	c.*3259T>C		3_prime_UTR_variant	4/4	ENST00000619898.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK4	ENST00000233027.10	c.*706A>G		3_prime_UTR_variant	16/16	1	NM_003157.6	P2
SPCS1	ENST00000619898.5	c.*3259T>C		3_prime_UTR_variant	4/4	1	NM_014041.5	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59721 AN: 151922 Hom.: 12652 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.422 AC: 178 AN: 422 Hom.: 39 Cov.: 0 AF XY: 0.418 AC XY: 107 AN XY: 256

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.393 AC: 59735 AN: 152042 Hom.: 12649 Cov.: 33 AF XY: 0.399 AC XY: 29671 AN XY: 74324

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.393

Alfa AF: 0.413 Hom.: 1719

Bravo AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	14
Dann	Benign	0.83

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: rs11235; hg19: chr3-52745087; COSMIC: COSV51777994; COSMIC: COSV51777994;