Variant 19-55306318-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_032430.2(BRSK1):c.1957G>A(p.Gly653Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,982 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

BRSK1
NM_032430.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.04

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 -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, BRSK1

BP4

Computational evidence support a benign effect (MetaRNN=0.23078427).

BS2

High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRSK1	NM_032430.2 linkuse as main transcript	c.1957G>A	p.Gly653Ser	missense_variant	17/19	ENST00000309383.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRSK1	ENST00000309383.6 linkuse as main transcript	c.1957G>A	p.Gly653Ser	missense_variant	17/19	1	NM_032430.2	P1	Q8TDC3-1
BRSK1	ENST00000590333.5 linkuse as main transcript	c.2005G>A	p.Gly669Ser	missense_variant	19/21	1			Q8TDC3-2
BRSK1	ENST00000326848.7 linkuse as main transcript	c.1042G>A	p.Gly348Ser	missense_variant	9/11	5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251256

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000808

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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 21, 2023

The c.1957G>A (p.G653S) alteration is located in exon 17 (coding exon 17) of the BRSK1 gene. This alteration results from a G to A substitution at nucleotide position 1957, causing the glycine (G) at amino acid position 653 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

0.041

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

Sift4G

Benign

0.076

T;T;D

Polyphen

0.97

D;P;.

Vest4

0.39

MVP

0.78

MPC

1.5

ClinPred

0.63

GERP RS

5.1

Varity_R

0.46

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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