19-55304833-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_032430.2(BRSK1):c.1630G>A(p.Val544Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000288 in 1,599,046 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
BRSK1
NM_032430.2 missense
NM_032430.2 missense
Scores
3
11
Clinical Significance
Conservation
PhyloP100: 4.15
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 made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, BRSK1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09253234).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRSK1 | NM_032430.2 | c.1630G>A | p.Val544Ile | missense_variant | 14/19 | ENST00000309383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRSK1 | ENST00000309383.6 | c.1630G>A | p.Val544Ile | missense_variant | 14/19 | 1 | NM_032430.2 | P1 | |
BRSK1 | ENST00000590333.5 | c.1678G>A | p.Val560Ile | missense_variant | 16/21 | 1 | |||
BRSK1 | ENST00000326848.7 | c.715G>A | p.Val239Ile | missense_variant | 6/11 | 5 | |||
BRSK1 | ENST00000588584.1 | n.346G>A | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152112Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000270 AC: 39AN: 1446934Hom.: 0 Cov.: 35 AF XY: 0.0000264 AC XY: 19AN XY: 719304
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.1630G>A (p.V544I) alteration is located in exon 14 (coding exon 14) of the BRSK1 gene. This alteration results from a G to A substitution at nucleotide position 1630, causing the valine (V) at amino acid position 544 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MutPred
0.33
.;Gain of MoRF binding (P = 0.142);.;
MVP
MPC
0.73
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at