Genetic Variant NM_020778.5:c.-83C>T (chr15-84817370-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020778.5(ALPK3):c.-83C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,073,260 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: not found (cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

ALPK3
NM_020778.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.942

Publications

1 publications found

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 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

ALPK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12005487).

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.-83C>T		5_prime_UTR	Exon 1 of 14	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.-83C>T		5_prime_UTR	Exon 1 of 14	ENSP00000258888.6	Q96L96
	ALPK3	ENST00000934403.1		c.-83C>T		5_prime_UTR	Exon 1 of 13	ENSP00000604462.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000373

AC:

AN:

1073260

Hom.:

Cov.:

AF XY:

0.00000591

AC XY:

AN XY:

507924

show subpopulations

African (AFR)

AF:

0.0000448

AC:

AN:

22314

American (AMR)

AF:

0.00

AC:

AN:

7904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13682

East Asian (EAS)

AF:

0.00

AC:

AN:

25204

South Asian (SAS)

AF:

0.00

AC:

AN:

20380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2852

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

916904

Other (OTH)

AF:

0.0000467

AC:

AN:

42818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.38

M_CAP

Benign

0.043

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.94

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.57

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Benign

0.12

Polyphen

0.95

Vest4

0.095

MutPred

0.40

Gain of sheet (P = 0.0125)

MVP

0.60

MPC

1.1

ClinPred

0.44

GERP RS

0.15

PromoterAI

-0.23

Neutral

(source)

Varity_R

0.077

gMVP

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over