Variant 15-84817363-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020778.5(ALPK3):c.-90G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,229,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ALPK3
NM_020778.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21584976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK3	NM_020778.5 linkuse as main transcript	c.-90G>A		5_prime_UTR_variant	1/14	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.-90G>A		5_prime_UTR_variant	1/14	1	NM_020778.5	ENSP00000258888	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000176

AC:

AN:

1077712

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

510274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.0000232

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151310

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73856

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2024

The p.A173T variant (also known as c.517G>A), located in coding exon 1 of the ALPK3 gene, results from a G to A substitution at nucleotide position 517. The alanine at codon 173 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.32

REVEL

Benign

0.063

Sift

Uncertain

0.015

Sift4G

Benign

0.12

Polyphen

0.76

Vest4

0.10

MutPred

0.34

Loss of helix (P = 0.0068);

MVP

0.53

MPC

1.0

ClinPred

0.31

GERP RS

2.5

Varity_R

0.083

gMVP

0.084

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