Genetic Variant STK32C:p.Pro474Leu (chr10-132208050-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_173575.4(STK32C):c.1421C>T(p.Pro474Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,158,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

Publications

0 publications found

Variant links:

Genes affected

STK32C (HGNC:21332): (serine/threonine kinase 32C) The protein encoded by this gene is a member of the serine/threonine protein kinase family. It is thought that this family member is functional in brain due to its high expression levels there. DNA methylation differences have been found in this gene in monozygotic twins that are discordant for adolescent depression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

STK32C 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=0.109268695).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173575.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK32C	NM_173575.4	MANE Select	c.1421C>T	p.Pro474Leu	missense	Exon 12 of 12	NP_775846.2
STK32C	NM_001318878.2		c.1460C>T	p.Pro487Leu	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
STK32C	NM_001318879.2		c.1070C>T	p.Pro357Leu	missense	Exon 12 of 12	NP_001305808.1	Q86UX6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK32C	ENST00000298630.8	TSL:1 MANE Select	c.1421C>T	p.Pro474Leu	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5	TSL:1	c.1070C>T	p.Pro357Leu	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000916800.1		c.1445C>T	p.Pro482Leu	missense	Exon 12 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000259

AC:

AN:

1158792

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

555228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24916

American (AMR)

AF:

0.00

AC:

AN:

17086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15242

East Asian (EAS)

AF:

0.00

AC:

AN:

30452

South Asian (SAS)

AF:

0.00

AC:

AN:

26744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4198

European-Non Finnish (NFE)

AF:

0.00000314

AC:

AN:

954348

Other (OTH)

AF:

0.00

AC:

AN:

46194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.78

M_CAP

Benign

0.036

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

PhyloP100

-0.085

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

REVEL

Benign

0.055

Sift

Uncertain

0.019

Sift4G

Uncertain

0.059

Polyphen

0.56

Vest4

0.11

MVP

0.71

MPC

0.25

ClinPred

0.18

GERP RS

2.5

Varity_R

0.067

gMVP

0.20

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over