15-84827366-C-G

Position:

• chr15-84827366-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000258888.6(ALPK3):​c.183-118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,436,426 control chromosomes in the GnomAD database, including 470,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54301 hom., cov: 34)
  • Exomes 𝑓: 0.80 (415964 hom.)
• Consequence: ALPK3 ENST00000258888.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.553

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-84827366-C-G is Benign according to our data. Variant chr15-84827366-C-G is described in ClinVar as [Benign]. Clinvar id is 678441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK3	NM_020778.5	c.183-118C>G		intron_variant		ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6	c.183-118C>G		intron_variant		1	NM_020778.5	ENSP00000258888	P1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127977 AN: 152142 Hom.: 54250 Cov.: 34

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.804 AC: 1031902 AN: 1284166 Hom.: 415964 AF XY: 0.803 AC XY: 511749 AN XY: 637328

Gnomad4 AFR exome AF: 0.957

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.841 AC: 128081 AN: 152260 Hom.: 54301 Cov.: 34 AF XY: 0.837 AC XY: 62322 AN XY: 74442

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.819

Alfa AF: 0.832 Hom.: 6565

Bravo AF: 0.846

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.6
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs891286; hg19: chr15-85370597;