15-84818746-G-T

Position:

• chr15-84818746-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020778.5(ALPK3):​c.143+1151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,064 control chromosomes in the GnomAD database, including 22,904 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 0.54 (22904 hom., cov: 33)
• Consequence: ALPK3 NM_020778.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPK3	NM_020778.5	c.143+1151G>T		intron_variant		ENST00000258888.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPK3	ENST00000258888.6	c.143+1151G>T		intron_variant		1	NM_020778.5	P1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81917 AN: 151946 Hom.: 22865 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 82013 AN: 152064 Hom.: 22904 Cov.: 33 AF XY: 0.540 AC XY: 40169 AN XY: 74328

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.501

Alfa AF: 0.482 Hom.: 9819

Bravo AF: 0.548

Asia WGS AF: 0.664 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.91

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: rs2879828; hg19: chr15-85361977;