Genetic Variant STK32C:p.Pro463His (chr10-132208083-G-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.1388C>A(p.Pro463His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,311,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.905

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=0.05096087).

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.1388C>A	p.Pro463His	missense	Exon 12 of 12	NP_775846.2
STK32C	NM_001318878.2		c.1427C>A	p.Pro476His	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
STK32C	NM_001318879.2		c.1037C>A	p.Pro346His	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.1388C>A	p.Pro463His	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5	TSL:1	c.1037C>A	p.Pro346His	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000916800.1		c.1412C>A	p.Pro471His	missense	Exon 12 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000259

AC:

AN:

115706

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000318

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:

0.0000121

AC:

AN:

1158822

Hom.:

Cov.:

AF XY:

0.00000901

AC XY:

AN XY:

554846

show subpopulations

African (AFR)

AF:

0.000562

AC:

AN:

24914

American (AMR)

AF:

0.00

AC:

AN:

17334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15274

East Asian (EAS)

AF:

0.00

AC:

AN:

30456

South Asian (SAS)

AF:

0.00

AC:

AN:

26732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4534

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

953524

Other (OTH)

AF:

0.00

AC:

AN:

46236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.000125

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41480

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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:

0.000132

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000355

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

0.089

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0040

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.40

M_CAP

Benign

0.024

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

PhyloP100

0.91

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.99

REVEL

Benign

0.086

Sift

Uncertain

0.0040

Sift4G

Benign

0.068

Polyphen

0.012

Vest4

0.12

MVP

0.62

MPC

0.26

ClinPred

0.049

GERP RS

1.7

Varity_R

0.10

gMVP

0.16

Mutation Taster

=91/9

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