chr13-52127646-T-C

Variant names:

• chr13-52127646-T-C
• rs1886543
• NM_001365552.1:c.-74A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK5	NM_001365552.1	MANE Select	c.-74A>G		5_prime_UTR	Exon 2 of 24	NP_001352481.1
	NEK5	NM_199289.3		c.-74A>G		5_prime_UTR	Exon 2 of 22	NP_954983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK5	ENST00000684899.1	MANE Select	c.-74A>G		5_prime_UTR	Exon 2 of 24	ENSP00000509632.1
	NEK5	ENST00000355568.8	TSL:1	c.-74A>G		5_prime_UTR	Exon 2 of 22	ENSP00000347767.4
	NEK5	ENST00000647945.2		c.-74A>G		5_prime_UTR	Exon 2 of 25	ENSP00000497892.1

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

African (AFR) AF: 0.307 AC: 3432 AN: 11194

American (AMR) AF: 0.643 AC: 9026 AN: 14032

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 8597 AN: 12540

East Asian (EAS) AF: 0.560 AC: 16156 AN: 28828

South Asian (SAS) AF: 0.515 AC: 19036 AN: 36990

European-Finnish (FIN) AF: 0.694 AC: 20840 AN: 30050

Middle Eastern (MID) AF: 0.678 AC: 1800 AN: 2656

European-Non Finnish (NFE) AF: 0.679 AC: 166846 AN: 245578

Other (OTH) AF: 0.646 AC: 15309 AN: 23704

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

African (AFR) AF: 0.311 AC: 12885 AN: 41464

American (AMR) AF: 0.632 AC: 9667 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2386 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3102 AN: 5178

South Asian (SAS) AF: 0.527 AC: 2541 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7371 AN: 10574

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46490 AN: 67978

Other (OTH) AF: 0.626 AC: 1321 AN: 2110

Alfa AF: 0.630 Hom.: 65041

Bravo AF: 0.557

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		-0.24
PromoterAI		0.032	Neutral
Mutation Taster		=300/0	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: rs1886543; hg19: chr13-52701782;