Variant chr15-84858449-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000258888.6(ALPK3):c.3711C>T(p.Asp1237=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,566,998 control chromosomes in the GnomAD database, including 3,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 355 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3056 hom. )

Consequence

ALPK3
ENST00000258888.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.852

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-84858449-C-T is Benign according to our data. Variant chr15-84858449-C-T is described in ClinVar as [Benign]. Clinvar id is 384683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-84858449-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.852 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK3	NM_020778.5 linkuse as main transcript	c.3711C>T	p.Asp1237=	synonymous_variant	6/14	ENST00000258888.6	NP_065829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6 linkuse as main transcript	c.3711C>T	p.Asp1237=	synonymous_variant	6/14	1	NM_020778.5	ENSP00000258888	P1

Frequencies

GnomAD3 genomes

AF:

0.0670

AC:

10184

AN:

151918

Hom.:

355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.0779

Gnomad SAS

AF:

0.0262

Gnomad FIN

AF:

0.0619

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0697

Gnomad OTH

AF:

0.0607

GnomAD3 exomes

AF:

0.0606

AC:

10749

AN:

177506

Hom.:

377

AF XY:

0.0584

AC XY:

5573

AN XY:

95392

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.0576

Gnomad ASJ exome

AF:

0.0388

Gnomad EAS exome

AF:

0.0804

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0618

Gnomad NFE exome

AF:

0.0701

Gnomad OTH exome

AF:

0.0605

GnomAD4 exome

AF:

0.0646

AC:

91404

AN:

1414962

Hom.:

3056

Cov.:

AF XY:

0.0635

AC XY:

44422

AN XY:

699956

show subpopulations

Gnomad4 AFR exome

AF:

0.0694

Gnomad4 AMR exome

AF:

0.0584

Gnomad4 ASJ exome

AF:

0.0366

Gnomad4 EAS exome

AF:

0.0820

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.0641

Gnomad4 NFE exome

AF:

0.0677

Gnomad4 OTH exome

AF:

0.0684

GnomAD4 genome

AF:

0.0670

AC:

10189

AN:

152036

Hom.:

355

Cov.:

AF XY:

0.0642

AC XY:

4772

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.0613

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.0779

Gnomad4 SAS

AF:

0.0262

Gnomad4 FIN

AF:

0.0619

Gnomad4 NFE

AF:

0.0697

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0662

Hom.:

143

Bravo

AF:

0.0687

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 10, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2016	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, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 24, 2018	p.Asp1439Asp in exon 6 of ALPK3: This variant is not expected to have clinical s ignificance because it has been identified in 10.6% (3091/29048) of total chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35931910). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

ALPK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.0

DANN

Benign

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over