Genetic Variant NM_020778.5:c.-78A>G (chr15-84817375-A-G) – 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.-78A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALPK3
NM_020778.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

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:

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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=0.07023734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK3	NM_020778.5 link	c.-78A>G		5_prime_UTR_variant	Exon 1 of 14	ENST00000258888.6	NP_065829.4	Q96L96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK3	ENST00000258888.6 link	c.-78A>G		5_prime_UTR_variant	Exon 1 of 14	1	NM_020778.5	ENSP00000258888.6		Q96L96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1072122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

507448

African (AFR)

AF:

0.00

AC:

AN:

22258

American (AMR)

AF:

0.00

AC:

AN:

7820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13586

East Asian (EAS)

AF:

0.00

AC:

AN:

24974

South Asian (SAS)

AF:

0.00

AC:

AN:

20450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2846

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

916240

Other (OTH)

AF:

0.00

AC:

AN:

42748

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.50

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.81

REVEL

Benign

0.086

Sift

Benign

0.090

Sift4G

Benign

0.35

Polyphen

0.049

Vest4

0.15

MutPred

0.41

Loss of methylation at R177 (P = 0.0022);

MVP

0.30

MPC

1.3

ClinPred

0.052

GERP RS

-3.9

PromoterAI

0.13

Neutral

(source)

Varity_R

0.12

gMVP

0.18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over