10-132224463-C-T

Variant names:

• chr10-132224463-C-T
• rs577074026
• NM_173575.4:c.937G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0397155).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32C	NM_173575.4	MANE Select	c.937G>A	p.Val313Met	missense	Exon 8 of 12	NP_775846.2
	STK32C	NM_001318878.2		c.976G>A	p.Val326Met	missense	Exon 8 of 12	NP_001305807.1	B7Z7J1
	STK32C	NM_001318879.2		c.586G>A	p.Val196Met	missense	Exon 8 of 12	NP_001305808.1	Q86UX6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK32C	ENST00000298630.8	TSL:1 MANE Select	c.937G>A	p.Val313Met	missense	Exon 8 of 12	ENSP00000298630.3	Q86UX6-1
	STK32C	ENST00000368622.5	TSL:1	c.586G>A	p.Val196Met	missense	Exon 8 of 12	ENSP00000357611.1	Q86UX6-2
	STK32C	ENST00000916800.1		c.961G>A	p.Val321Met	missense	Exon 8 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152112 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000145 AC: 27 AN: 186426 AF XY: 0.000182

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 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.: 0 Cov.: 31 AF XY: 0.000101 AC XY: 71 AN XY: 702258

African (AFR) AF: 0.000122 AC: 4 AN: 32754

American (AMR) AF: 0.000105 AC: 4 AN: 38220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25320

East Asian (EAS) AF: 0.000212 AC: 8 AN: 37806

South Asian (SAS) AF: 0.000161 AC: 13 AN: 80592

European-Finnish (FIN) AF: 0.0000600 AC: 3 AN: 50040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.0000889 AC: 97 AN: 1090804

Other (OTH) AF: 0.000119 AC: 7 AN: 58926

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74416

African (AFR) AF: 0.0000482 AC: 2 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000992 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.000109 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.88	L
PhyloP100		4.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.026
Sift	Benign	0.070	T
Sift4G	Benign	0.10	T
Polyphen		0.018	B
Vest4		0.32
MVP		0.62
MPC		0.27
ClinPred		0.042	T
GERP RS		3.1
Varity_R		0.17
gMVP		0.58
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs577074026; hg19: chr10-134037967; COSMIC: COSV53843633; COSMIC: COSV53843633;