15-84836265-T-C

Variant names:

• chr15-84836265-T-C
• rs7164787
• NM_020778.5:c.305-2715T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020778.5(ALPK3):​c.305-2715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,970 control chromosomes in the GnomAD database, including 18,758 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 0.48 (18758 hom., cov: 32)
• Consequence: ALPK3 NM_020778.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 9 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, AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen
• cardiomyopathy, familial hypertrophic 27

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK3	NM_020778.5	MANE Select	c.305-2715T>C		intron	N/A	NP_065829.4	Q96L96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK3	ENST00000258888.6	TSL:1 MANE Select	c.305-2715T>C		intron	N/A	ENSP00000258888.6	Q96L96
	ALPK3	ENST00000934403.1		c.266-2715T>C		intron	N/A	ENSP00000604462.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72150 AN: 151852 Hom.: 18712 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.475 AC: 72253 AN: 151970 Hom.: 18758 Cov.: 32 AF XY: 0.479 AC XY: 35581 AN XY: 74266

African (AFR) AF: 0.666 AC: 27583 AN: 41416

American (AMR) AF: 0.462 AC: 7066 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4083 AN: 5158

South Asian (SAS) AF: 0.515 AC: 2487 AN: 4830

European-Finnish (FIN) AF: 0.373 AC: 3931 AN: 10542

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24561 AN: 67952

Other (OTH) AF: 0.432 AC: 911 AN: 2110

Alfa AF: 0.398 Hom.: 40461

Bravo AF: 0.489

Asia WGS AF: 0.653 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		-1.1
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: rs7164787; hg19: chr15-85379496;