Variant 19-55304732-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032430.2(BRSK1):c.1529G>T(p.Arg510Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,520,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

BRSK1
NM_032430.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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]

BRSK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058342606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRSK1	NM_032430.2 linkuse as main transcript	c.1529G>T	p.Arg510Leu	missense_variant	14/19	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6 linkuse as main transcript	c.1529G>T	p.Arg510Leu	missense_variant	14/19	1	NM_032430.2	ENSP00000310649	P1	Q8TDC3-1
BRSK1	ENST00000590333.5 linkuse as main transcript	c.1577G>T	p.Arg526Leu	missense_variant	16/21	1		ENSP00000468190		Q8TDC3-2
BRSK1	ENST00000326848.7 linkuse as main transcript	c.614G>T	p.Arg205Leu	missense_variant	6/11	5		ENSP00000320853
BRSK1	ENST00000588584.1 linkuse as main transcript	n.245G>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000732

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370136

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150832

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73624

show subpopulations

Gnomad4 AFR

AF:

0.0000732

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000101

AC:

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

Apr 26, 2024

The c.1529G>T (p.R510L) alteration is located in exon 14 (coding exon 14) of the BRSK1 gene. This alteration results from a G to T substitution at nucleotide position 1529, causing the arginine (R) at amino acid position 510 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.058

.;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

.;N;.

MutationTaster

Benign

0.59

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.25

.;N;N

REVEL

Benign

0.057

Sift

Benign

0.43

.;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.14

MutPred

0.36

.;Loss of methylation at R510 (P = 0.0365);.;

MVP

0.22

MPC

1.2

ClinPred

0.54

GERP RS

4.2

Varity_R

0.079

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over