rs12430077

Variant names:

• chr13-52035072-T-C
• rs12430077
• NM_001365552.1:c.*1876A>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.*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
• Publications: 3 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]

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]

ALG11 Gene-Disease associations (from GenCC):

• ALG11-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Ambry Genetics, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEK5	NM_001365552.1	c.*1876A>G		3_prime_UTR_variant	Exon 24 of 24	ENST00000684899.1	NP_001352481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK5	ENST00000684899.1	c.*1876A>G		3_prime_UTR_variant	Exon 24 of 24		NM_001365552.1	ENSP00000509632.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.00381 AC: 157 AN: 41230

American (AMR) AF: 0.0617 AC: 940 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.195 AC: 1001 AN: 5132

South Asian (SAS) AF: 0.00961 AC: 46 AN: 4786

European-Finnish (FIN) AF: 0.0776 AC: 814 AN: 10484

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00596 AC: 405 AN: 67924

Other (OTH) AF: 0.0252 AC: 53 AN: 2104

Alfa AF: 0.0265 Hom.: 65

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
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs12430077; hg19: chr13-52609208;