19-55304765-T-C

Variant summary

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

The NM_032430.2(BRSK1):​c.1562T>C​(p.Leu521Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,604 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: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

BRSK1
NM_032430.2 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

Publications

0 publications found
Variant links:
Genes affected
BRSK1 (HGNC:18994): (BR serine/threonine kinase 1) Enables magnesium ion binding activity; protein serine/threonine kinase activity; and tau-protein kinase activity. Involved in mitotic G2 DNA damage checkpoint signaling and protein phosphorylation. Acts upstream of or within G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; and response to UV. Located in cell junction; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.2156995).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRSK1NM_032430.2 linkc.1562T>C p.Leu521Pro missense_variant Exon 14 of 19 ENST00000309383.6 NP_115806.1 Q8TDC3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRSK1ENST00000309383.6 linkc.1562T>C p.Leu521Pro missense_variant Exon 14 of 19 1 NM_032430.2 ENSP00000310649.1 Q8TDC3-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1394604
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
689404
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31654
American (AMR)
AF:
0.00
AC:
0
AN:
35726
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24994
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36042
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80238
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
41126
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4226
European-Non Finnish (NFE)
AF:
9.24e-7
AC:
1
AN:
1082690
Other (OTH)
AF:
0.00
AC:
0
AN:
57908
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 30, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1562T>C (p.L521P) alteration is located in exon 14 (coding exon 14) of the BRSK1 gene. This alteration results from a T to C substitution at nucleotide position 1562, causing the leucine (L) at amino acid position 521 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Pathogenic
27
DANN
Uncertain
0.97
DEOGEN2
Benign
0.17
.;T;T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.58
T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;.
PhyloP100
5.9
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.2
.;N;N
REVEL
Benign
0.11
Sift
Benign
0.12
.;T;D
Sift4G
Benign
0.15
T;T;T
Polyphen
0.90
P;P;.
Vest4
0.27
MutPred
0.40
.;Gain of relative solvent accessibility (P = 0.005);.;
MVP
0.54
MPC
2.1
ClinPred
0.73
D
GERP RS
4.9
Varity_R
0.35
gMVP
0.21
Mutation Taster
=52/48
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

hg19: chr19-55816133; API