NM_020778.5:c.143+1151G>T

Variant names:

• chr15-84818746-G-T
• rs2879828
• NM_020778.5:c.143+1151G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ALPK3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cardiomyopathy, familial hypertrophic 27

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020778.5. 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
	ALPK3	NM_020778.5	MANE Select	c.143+1151G>T		intron	N/A	NP_065829.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK3	ENST00000258888.6	TSL:1 MANE Select	c.143+1151G>T		intron	N/A	ENSP00000258888.6

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

African (AFR) AF: 0.675 AC: 28009 AN: 41470

American (AMR) AF: 0.530 AC: 8094 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4086 AN: 5172

South Asian (SAS) AF: 0.534 AC: 2577 AN: 4822

European-Finnish (FIN) AF: 0.456 AC: 4816 AN: 10550

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31412 AN: 67984

Other (OTH) AF: 0.501 AC: 1055 AN: 2106

Alfa AF: 0.483 Hom.: 10840

Bravo AF: 0.548

Asia WGS AF: 0.664 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2879828; hg19: chr15-85361977;