chr15-84872155-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020778.5(ALPK3):​c.*3699T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,276 control chromosomes in the GnomAD database, including 2,831 homozygotes. 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: 𝑓 0.17 ( 2830 hom., cov: 34)
Exomes 𝑓: 0.16 ( 1 hom. )

Consequence

ALPK3
NM_020778.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.538

Publications

16 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 Classification: DEFINITIVE Submitted by: ClinGen
  • cardiomyopathy, familial hypertrophic 27
    Inheritance: AR, AD, SD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALPK3NM_020778.5 linkc.*3699T>C 3_prime_UTR_variant Exon 14 of 14 ENST00000258888.6 NP_065829.4 Q96L96

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALPK3ENST00000258888.6 linkc.*3699T>C 3_prime_UTR_variant Exon 14 of 14 1 NM_020778.5 ENSP00000258888.6 Q96L96

Frequencies

GnomAD3 genomes
AF:
0.171
AC:
26007
AN:
152108
Hom.:
2833
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0420
Gnomad AMI
AF:
0.240
Gnomad AMR
AF:
0.201
Gnomad ASJ
AF:
0.235
Gnomad EAS
AF:
0.131
Gnomad SAS
AF:
0.150
Gnomad FIN
AF:
0.261
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.228
Gnomad OTH
AF:
0.198
GnomAD4 exome
AF:
0.160
AC:
8
AN:
50
Hom.:
1
Cov.:
0
AF XY:
0.190
AC XY:
8
AN XY:
42
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.174
AC:
8
AN:
46
Other (OTH)
AF:
0.00
AC:
0
AN:
2
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.408
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.171
AC:
25998
AN:
152226
Hom.:
2830
Cov.:
34
AF XY:
0.171
AC XY:
12722
AN XY:
74420
show subpopulations
African (AFR)
AF:
0.0420
AC:
1743
AN:
41546
American (AMR)
AF:
0.200
AC:
3067
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.235
AC:
816
AN:
3468
East Asian (EAS)
AF:
0.130
AC:
674
AN:
5180
South Asian (SAS)
AF:
0.151
AC:
729
AN:
4828
European-Finnish (FIN)
AF:
0.261
AC:
2760
AN:
10594
Middle Eastern (MID)
AF:
0.276
AC:
81
AN:
294
European-Non Finnish (NFE)
AF:
0.228
AC:
15495
AN:
67992
Other (OTH)
AF:
0.196
AC:
414
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1097
2194
3291
4388
5485
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
278
556
834
1112
1390
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.214
Hom.:
6807
Bravo
AF:
0.163
Asia WGS
AF:
0.146
AC:
507
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
2.4
DANN
Benign
0.41
PhyloP100
-0.54
Mutation Taster
=100/0
polymorphism (auto)

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: rs12900463; hg19: chr15-85415386; API