15-84817370-CG-C

Variant names:

• chr15-84817370-CG-C
• NM_020778.5:c.-80delG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020778.5(ALPK3):​c.-80delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,073,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: ALPK3 NM_020778.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.662

Genes affected

ALPK3 (HGNC:17574): (alpha kinase 3) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in cardiac muscle cell development. Predicted to be active in nucleus. Implicated in hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.-80delG		5_prime_UTR_variant	Exon 1 of 14	ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6	c.-80delG		5_prime_UTR_variant	Exon 1 of 14	1	NM_020778.5	ENSP00000258888.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000373 AC: 4 AN: 1073260 Hom.: 0 Cov.: 50 AF XY: 0.00000591 AC XY: 3 AN XY: 507924

African (AFR) AF: 0.00 AC: 0 AN: 22314

American (AMR) AF: 0.00 AC: 0 AN: 7904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13682

East Asian (EAS) AF: 0.00 AC: 0 AN: 25204

South Asian (SAS) AF: 0.00 AC: 0 AN: 20380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2852

European-Non Finnish (NFE) AF: 0.00000436 AC: 4 AN: 916904

Other (OTH) AF: 0.00 AC: 0 AN: 42818

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 04, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Gly176Alafs*135) in the ALPK3 gene. It is unclear whether it will result in an absent or disrupted protein product because an in-frame methionine located at codon 203 has the potential to rescue this truncating variant. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALPK3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66

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

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Other links and lift over

hg19: chr15-85360601;