15-84817358-G-GAGC

Variant names:

• chr15-84817358-G-GAGC
• NM_020778.5:c.-94_-92dupAGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020778.5(ALPK3):​c.-94_-92dupAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,080,666 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: 9.3e-7 (0 hom.)
• Consequence: ALPK3 NM_020778.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.-94_-92dupAGC		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	c.-94_-92dupAGC		5_prime_UTR_variant	Exon 1 of 14	1	NM_020778.5	ENSP00000258888.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1080666 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 511752

Gnomad4 AFR exome AF: 0.0000443

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.513_515dup, results in the insertion of 1 amino acid(s) of the ALPK3 protein (p.Ala175dup), but otherwise preserves the integrity of the reading frame. 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. ClinVar contains an entry for this variant (Variation ID: 1481586). 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

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-85360589;