dbSNP rs751535819: BRSK1:p.Arg510His (chr19-55304732-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032430.2(BRSK1):c.1529G>A(p.Arg510His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,370,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R510L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

BRSK1
NM_032430.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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]

BRSK1 links:

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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=0.10028151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK1	NM_032430.2 link	c.1529G>A	p.Arg510His	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
BRSK1	ENST00000309383.6 link	c.1529G>A	p.Arg510His	missense_variant	Exon 14 of 19	1	NM_032430.2	ENSP00000310649.1		Q8TDC3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

118726

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1370136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30354

American (AMR)

AF:

0.00

AC:

AN:

32584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23900

East Asian (EAS)

AF:

0.00

AC:

AN:

35222

South Asian (SAS)

AF:

0.00

AC:

AN:

77310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1072428

Other (OTH)

AF:

0.00

AC:

AN:

56966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000101

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

.;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.0011

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.85

D;D;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.

PhyloP100

1.7

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.12

.;N;N

REVEL

Benign

0.043

Sift

Benign

0.12

.;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.075

MutPred

0.37

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

MVP

0.30

MPC

1.5

ClinPred

0.89

GERP RS

4.2

Varity_R

0.048

gMVP

0.092

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over