rs2062153021

Variant names:

• chr10-132208041-C-A
• rs2062153021
• NM_173575.4:c.1430G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173575.4(STK32C):​c.1430G>T​(p.Gly477Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000863 in 1,158,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 8.6e-7 (0 hom.)
• Consequence: STK32C NM_173575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24928111).

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.1430G>T	p.Gly477Val	missense	Exon 12 of 12	NP_775846.2
	STK32C	NM_001318878.2		c.1469G>T	p.Gly490Val	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
	STK32C	NM_001318879.2		c.1079G>T	p.Gly360Val	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.1430G>T	p.Gly477Val	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
	STK32C	ENST00000368622.5	TSL:1	c.1079G>T	p.Gly360Val	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
	STK32C	ENST00000916800.1		c.1454G>T	p.Gly485Val	missense	Exon 12 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 8.63e-7 AC: 1 AN: 1158550 Hom.: 0 Cov.: 31 AF XY: 0.00000180 AC XY: 1 AN XY: 555146

African (AFR) AF: 0.00 AC: 0 AN: 24914

American (AMR) AF: 0.00 AC: 0 AN: 17028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15238

East Asian (EAS) AF: 0.00 AC: 0 AN: 30454

South Asian (SAS) AF: 0.00 AC: 0 AN: 26734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4064

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 954348

Other (OTH) AF: 0.00 AC: 0 AN: 46194

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Benign	0.0071	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0096	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.20	T
Polyphen		0.98	D
Vest4		0.22
MVP		0.79
MPC		0.77
ClinPred		0.88	D
GERP RS		4.5
Varity_R		0.24
gMVP		0.18
Mutation Taster		=90/10	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: rs2062153021; hg19: chr10-134021545;