rs12430077

Positions:

• chr13-52035072-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.*1876A>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 0.0226 in 151,562 control chromosomes in the GnomAD database, including 182 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 0.023 (181 hom., cov: 31)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: NEK5 NM_001365552.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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]

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK5	NM_001365552.1	c.*1876A>G		3_prime_UTR_variant	24/24	ENST00000684899.1	NP_001352481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK5	ENST00000684899.1	c.*1876A>G		3_prime_UTR_variant	24/24		NM_001365552.1	ENSP00000509632	P2

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3412 AN: 151440 Hom.: 180 Cov.: 31

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.00981

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00596

Gnomad OTH AF: 0.0235

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0226 AC: 3419 AN: 151556 Hom.: 181 Cov.: 31 AF XY: 0.0266 AC XY: 1972 AN XY: 74040

Gnomad4 AFR AF: 0.00381

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.00961

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.00596

Gnomad4 OTH AF: 0.0252

Alfa AF: 0.0216 Hom.: 14

Bravo AF: 0.0234

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.27
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12430077; hg19: chr13-52609208;