NM_173575.4:c.1385A>G

Variant names:

• chr10-132208086-T-C
• rs759091739
• NM_173575.4:c.1385A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173575.4(STK32C):​c.1385A>G​(p.Glu462Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000863 in 1,158,844 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: STK32C NM_173575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592
• Publications: 0 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=0.03857082).

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.1385A>G	p.Glu462Gly	missense	Exon 12 of 12	NP_775846.2
	STK32C	NM_001318878.2		c.1424A>G	p.Glu475Gly	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
	STK32C	NM_001318879.2		c.1034A>G	p.Glu345Gly	missense	Exon 12 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.1385A>G	p.Glu462Gly	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
	STK32C	ENST00000368622.5	TSL:1	c.1034A>G	p.Glu345Gly	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
	STK32C	ENST00000916800.1		c.1409A>G	p.Glu470Gly	missense	Exon 12 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.0000778 AC: 9 AN: 115732 AF XY: 0.0000639

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000514

GnomAD4 exome AF: 0.00000863 AC: 10 AN: 1158844 Hom.: 0 Cov.: 31 AF XY: 0.00000721 AC XY: 4 AN XY: 554878

African (AFR) AF: 0.00 AC: 0 AN: 24918

American (AMR) AF: 0.00 AC: 0 AN: 17330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15270

East Asian (EAS) AF: 0.000263 AC: 8 AN: 30460

South Asian (SAS) AF: 0.0000374 AC: 1 AN: 26712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4542

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 953536

Other (OTH) AF: 0.00 AC: 0 AN: 46250

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000800 AC: 9

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	0.062
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.59
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Sift	Benign	0.17	T
Sift4G	Benign	0.34	T
Polyphen		0.24	B
Vest4		0.20
MVP		0.71
MPC		0.27
ClinPred		0.086	T
GERP RS		3.9
Varity_R		0.050
gMVP		0.18
Mutation Taster		=91/9	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: rs759091739; hg19: chr10-134021590;