19-55303723-C-G

Variant names:

• chr19-55303723-C-G
• rs780991388
• NM_032430.2:c.1183C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032430.2(BRSK1):​c.1183C>G​(p.Pro395Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P395S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRSK1 NM_032430.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.1183C>G	p.Pro395Ala	missense_variant	Exon 12 of 19	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.1183C>G	p.Pro395Ala	missense_variant	Exon 12 of 19	1	NM_032430.2	ENSP00000310649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;T;.;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Benign	0.90	.;L;.;.
PhyloP100		7.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	.;D;.;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.011	.;D;.;D
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.97	D;P;.;.
Vest4		0.47
MutPred		0.33		.;Loss of glycosylation at P395 (P = 0.0057);.;.;
MVP		0.43
MPC		1.3
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.68
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs780991388; hg19: chr19-55815091;