Genetic Variant STK32C:p.Val313Met (chr10-132224463-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173575.4(STK32C):c.937G>A(p.Val313Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000922 in 1,572,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0397155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK32C	NM_173575.4 link	c.937G>A	p.Val313Met	missense_variant	Exon 8 of 12	ENST00000298630.8	NP_775846.2	Q86UX6-1A0A140VJW0B7Z7J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK32C	ENST00000298630.8 link	c.937G>A	p.Val313Met	missense_variant	Exon 8 of 12	1	NM_173575.4	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5 link	c.586G>A	p.Val196Met	missense_variant	Exon 8 of 12	1		ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000462160.5 link	n.754G>A		non_coding_transcript_exon_variant	Exon 8 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

186426

Hom.:

AF XY:

0.000182

AC XY:

AN XY:

99166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000496

Gnomad SAS exome

AF:

0.000247

Gnomad FIN exome

AF:

0.0000605

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000202

GnomAD4 exome

AF:

0.0000958

AC:

136

AN:

1420178

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

702258

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.000105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000212

Gnomad4 SAS exome

AF:

0.000161

Gnomad4 FIN exome

AF:

0.0000600

Gnomad4 NFE exome

AF:

0.0000889

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000992

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000109

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.937G>A (p.V313M) alteration is located in exon 8 (coding exon 8) of the STK32C gene. This alteration results from a G to A substitution at nucleotide position 937, causing the valine (V) at amino acid position 313 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.88

.;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.026

Sift

Benign

0.070

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.018

B;B

Vest4

0.32

MVP

0.62

MPC

0.27

ClinPred

0.042

GERP RS

3.1

Varity_R

0.17

gMVP

0.58

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