Variant 19-55304584-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000309383.6(BRSK1):c.1381G>T(p.Ala461Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,586,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BRSK1
ENST00000309383.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0550

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04132068).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRSK1	NM_032430.2 linkuse as main transcript	c.1381G>T	p.Ala461Ser	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.1381G>T	p.Ala461Ser	missense_variant	14/19	1	NM_032430.2	ENSP00000310649	P1	Q8TDC3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1433796

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

712040

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.0000740

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:

0.00000545

Gnomad4 OTH exome

AF:

0.0000676

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00000378

ExAC

AF:

0.00000833

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

Aug 09, 2021

The c.1381G>T (p.A461S) 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 1381, causing the alanine (A) at amino acid position 461 to be replaced by a serine (S). 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

0.064

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.063

.;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N;.

MutationTaster

Benign

0.58

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.40

.;N;N

REVEL

Benign

0.048

Sift

Benign

0.59

.;T;T

Sift4G

Benign

0.65

T;T;T

Polyphen

0.34

B;B;.

Vest4

0.14

MVP

0.42

MPC

0.72

ClinPred

0.064

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.066

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

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