13-52127646-T-C

Position:

• chr13-52127646-T-C

Variant summary

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

The NM_001365552.1(NEK5):​c.-74A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 557,660 control chromosomes in the GnomAD database, including 112,358 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 0.57 (26573 hom., cov: 32)
  • Exomes 𝑓: 0.64 (85785 hom.)
• Consequence: NEK5 NM_001365552.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

Genes affected

NEK5 (HGNC:7748): (NIMA related kinase 5) Predicted to enable ATP binding activity; metal ion binding activity; and protein kinase activity. Predicted to be involved in protein phosphorylation. Predicted to act upstream of or within positive regulation of cysteine-type endopeptidase activity and positive regulation of striated muscle cell differentiation. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK5	NM_001365552.1	c.-74A>G		5_prime_UTR_variant	2/24	ENST00000684899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK5	ENST00000684899.1	c.-74A>G		5_prime_UTR_variant	2/24		NM_001365552.1	P2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86472 AN: 151970 Hom.: 26569 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.644 AC: 261042 AN: 405572 Hom.: 85785 Cov.: 3 AF XY: 0.640 AC XY: 138066 AN XY: 215844

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.569 AC: 86494 AN: 152088 Hom.: 26573 Cov.: 32 AF XY: 0.572 AC XY: 42510 AN XY: 74354

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.626

Alfa AF: 0.664 Hom.: 43805

Bravo AF: 0.557

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
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: rs1886543; hg19: chr13-52701782;