GeneBe

rs1963370921

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020778.5(ALPK3):​c.-96G>A 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

1
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.102

Publications

0 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: AD, AR 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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05855006).

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ALPK3
NM_020778.5
MANE Select
c.-96G>A
5_prime_UTR
Exon 1 of 14NP_065829.4Q96L96

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ALPK3
ENST00000258888.6
TSL:1 MANE Select
c.-96G>A
5_prime_UTR
Exon 1 of 14ENSP00000258888.6Q96L96
ALPK3
ENST00000934403.1
c.-96G>A
5_prime_UTR
Exon 1 of 13ENSP00000604462.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1081646
Hom.:
0
Cov.:
50
AF XY:
0.00
AC XY:
0
AN XY:
512210
African (AFR)
AF:
0.00
AC:
0
AN:
22590
American (AMR)
AF:
0.00
AC:
0
AN:
8142
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14034
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25874
South Asian (SAS)
AF:
0.00
AC:
0
AN:
20830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
21436
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2910
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
922390
Other (OTH)
AF:
0.00
AC:
0
AN:
43440
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.0058
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.41
T
M_CAP
Pathogenic
0.34
D
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
PhyloP100
-0.10
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.82
N
REVEL
Benign
0.036
Sift
Benign
0.43
T
Sift4G
Benign
0.33
T
Polyphen
0.0020
B
Vest4
0.081
MutPred
0.37
Gain of methylation at G171 (P = 0.0056)
MVP
0.39
MPC
1.3
ClinPred
0.044
T
GERP RS
-1.4
PromoterAI
-0.094
Neutral
Varity_R
0.086
gMVP
0.17

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

Other links and lift over

dbSNP: rs1963370921; hg19: chr15-85360588; API