10-132222875-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173575.4(STK32C):​c.1105G>A​(p.Gly369Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,426,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16661972).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK32CNM_173575.4 linkc.1105G>A p.Gly369Ser missense_variant Exon 9 of 12 ENST00000298630.8 NP_775846.2 Q86UX6-1A0A140VJW0B7Z7J1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK32CENST00000298630.8 linkc.1105G>A p.Gly369Ser missense_variant Exon 9 of 12 1 NM_173575.4 ENSP00000298630.3 Q86UX6-1
STK32CENST00000368622.5 linkc.754G>A p.Gly252Ser missense_variant Exon 9 of 12 1 ENSP00000357611.1 Q86UX6-2
STK32CENST00000462160.5 linkn.922G>A non_coding_transcript_exon_variant Exon 9 of 13 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1426874
Hom.:
0
Cov.:
35
AF XY:
0.00000141
AC XY:
1
AN XY:
707492
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000267
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.11e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000251
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1105G>A (p.G369S) alteration is located in exon 9 (coding exon 9) of the STK32C gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the glycine (G) at amino acid position 369 to be replaced by a serine (S). 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
0.098
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Benign
0.90
DEOGEN2
Benign
0.030
.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.042
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.12
Sift
Benign
0.68
T;T
Sift4G
Benign
0.54
T;T
Polyphen
0.28
B;B
Vest4
0.46
MVP
0.35
MPC
0.23
ClinPred
0.29
T
GERP RS
3.9
Varity_R
0.15
gMVP
0.62

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.

Other links and lift over

dbSNP: rs749687889; hg19: chr10-134036379; API