Genetic Variant STK32C:p.Arg449Lys (chr10-132208125-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173575.4(STK32C):c.1346G>A(p.Arg449Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,310,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.589

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021570802).

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.1346G>A	p.Arg449Lys	missense	Exon 12 of 12	NP_775846.2
STK32C	NM_001318878.2		c.1385G>A	p.Arg462Lys	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
STK32C	NM_001318879.2		c.995G>A	p.Arg332Lys	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.1346G>A	p.Arg449Lys	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5	TSL:1	c.995G>A	p.Arg332Lys	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000916800.1		c.1370G>A	p.Arg457Lys	missense	Exon 12 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000435

AC:

AN:

114988

AF XY:

0.0000641

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000489

Gnomad OTH exome

AF:

0.000518

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1158444

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

554512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24914

American (AMR)

AF:

0.000749

AC:

AN:

17352

Ashkenazi Jewish (ASJ)

AF:

0.0000657

AC:

AN:

15232

East Asian (EAS)

AF:

0.00

AC:

AN:

30476

South Asian (SAS)

AF:

0.00

AC:

AN:

26514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39812

Middle Eastern (MID)

AF:

0.000658

AC:

AN:

4556

European-Non Finnish (NFE)

AF:

0.0000336

AC:

AN:

953376

Other (OTH)

AF:

0.000281

AC:

AN:

46212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.00104

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000627

AC:

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

0.076

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.20

M_CAP

Benign

0.024

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

-0.59

PrimateAI

Benign

0.42

PROVEAN

Benign

0.080

REVEL

Benign

0.029

Sift

Benign

0.61

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.059

MVP

0.30

MPC

0.23

ClinPred

0.015

GERP RS

-3.1

Varity_R

0.049

gMVP

0.15

Mutation Taster

=99/1

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over