10-132222886-C-A

Variant names:

• chr10-132222886-C-A
• rs1038609372
• NM_173575.4:c.1094G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173575.4(STK32C):​c.1094G>T​(p.Arg365Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,420,498 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: STK32C NM_173575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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]

ACMG classification

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=0.18292058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK32C	NM_173575.4	c.1094G>T	p.Arg365Met	missense_variant	Exon 9 of 12	ENST00000298630.8	NP_775846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK32C	ENST00000298630.8	c.1094G>T	p.Arg365Met	missense_variant	Exon 9 of 12	1	NM_173575.4	ENSP00000298630.3
STK32C	ENST00000368622.5	c.743G>T	p.Arg248Met	missense_variant	Exon 9 of 12	1		ENSP00000357611.1
STK32C	ENST00000462160.5	n.911G>T		non_coding_transcript_exon_variant	Exon 9 of 13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000563 AC: 8 AN: 1420498 Hom.: 0 Cov.: 35 AF XY: 0.00000710 AC XY: 5 AN XY: 703828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000731

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1094G>T (p.R365M) alteration is located in exon 9 (coding exon 9) of the STK32C gene. This alteration results from a G to T substitution at nucleotide position 1094, causing the arginine (R) at amino acid position 365 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	0.087
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.053
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.50	P;B
Vest4		0.30
MVP		0.34
MPC		0.26
ClinPred		0.61	D
GERP RS		2.8
Varity_R		0.099
gMVP		0.48

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

Other links and lift over

dbSNP: rs1038609372; hg19: chr10-134036390;