13-52127646-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365552.1(NEK5):​c.-74A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEK5 NM_001365552.1 5_prime_UTR_premature_start_codon_gain
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 24	NP_001352481.1
	NEK5	NM_001365552.1	MANE Select	c.-74A>T		5_prime_UTR	Exon 2 of 24	NP_001352481.1
	NEK5	NM_199289.3		c.-74A>T		5_prime_UTR_premature_start_codon_gain	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>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 24	ENSP00000509632.1
	NEK5	ENST00000355568.8	TSL:1	c.-74A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	ENSP00000347767.4
	NEK5	ENST00000684899.1	MANE Select	c.-74A>T		5_prime_UTR	Exon 2 of 24	ENSP00000509632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 406610 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 216442

African (AFR) AF: 0.00 AC: 0 AN: 11212

American (AMR) AF: 0.00 AC: 0 AN: 14064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12576

East Asian (EAS) AF: 0.00 AC: 0 AN: 28894

South Asian (SAS) AF: 0.00 AC: 0 AN: 37146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 246164

Other (OTH) AF: 0.00 AC: 0 AN: 23774

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.86
PhyloP100		-0.24
PromoterAI		-0.0014	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;