Variant 11-8436032-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001352389.2(STK33):c.1055A>C(p.Asp352Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,904 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

STK33
NM_001352389.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

STK33 (HGNC:14568): (serine/threonine kinase 33) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in mitotic DNA damage checkpoint signaling and protein autophosphorylation. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STK33 links:

STK33 (HGNC:):

STK33 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34123623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK33	NM_001352389.2 linkuse as main transcript	c.1055A>C	p.Asp352Ala	missense_variant	13/16	ENST00000687296.1	NP_001339318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK33	ENST00000687296.1 linkuse as main transcript	c.1055A>C	p.Asp352Ala	missense_variant	13/16		NM_001352389.2	ENSP00000509322.1		Q9BYT3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000436

AC:

AN:

229186

Hom.:

AF XY:

0.00000806

AC XY:

AN XY:

124034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000603

Gnomad SAS 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:

7.09e-7

AC:

AN:

1410904

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700926

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

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

Cov.:

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

Nov 08, 2024

The c.1055A>C (p.D352A) alteration is located in exon 11 (coding exon 9) of the STK33 gene. This alteration results from a A to C substitution at nucleotide position 1055, causing the aspartic acid (D) at amino acid position 352 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;T;T;T;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

.;.;T;T;T;T

M_CAP

Benign

0.056

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.96

L;L;L;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.9

D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.021

D;D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D;D

Polyphen

0.069

B;B;B;.;.;B

Vest4

0.45

MutPred

0.55

Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);.;.;.;

MVP

0.73

MPC

0.18

ClinPred

0.88

GERP RS

4.5

Varity_R

0.36

gMVP

0.56

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