10-132226815-G-A

Variant names:

• chr10-132226815-G-A
• rs74161742
• NM_173575.4:c.624C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173575.4(STK32C):​c.624C>T​(p.Arg208Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,612,986 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (164 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (156 hom.)
• Consequence: STK32C NM_173575.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.749
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-132226815-G-A is Benign according to our data. Variant chr10-132226815-G-A is described in ClinVar as Benign. ClinVar VariationId is 768402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.749 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

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.624C>T	p.Arg208Arg	synonymous	Exon 4 of 12	NP_775846.2
	STK32C	NM_001318878.2		c.663C>T	p.Arg221Arg	synonymous	Exon 4 of 12	NP_001305807.1	B7Z7J1
	STK32C	NM_001318879.2		c.273C>T	p.Arg91Arg	synonymous	Exon 4 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.624C>T	p.Arg208Arg	synonymous	Exon 4 of 12	ENSP00000298630.3	Q86UX6-1
	STK32C	ENST00000368622.5	TSL:1	c.273C>T	p.Arg91Arg	synonymous	Exon 4 of 12	ENSP00000357611.1	Q86UX6-2
	STK32C	ENST00000916800.1		c.624C>T	p.Arg208Arg	synonymous	Exon 4 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3888 AN: 152240 Hom.: 164 Cov.: 34

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00648 AC: 1622 AN: 250116 AF XY: 0.00455

Gnomad AFR exome AF: 0.0857

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000470

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00281 AC: 4109 AN: 1460628 Hom.: 156 Cov.: 35 AF XY: 0.00243 AC XY: 1769 AN XY: 726614

African (AFR) AF: 0.0894 AC: 2993 AN: 33480

American (AMR) AF: 0.00517 AC: 231 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52224

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000430 AC: 478 AN: 1111972

Other (OTH) AF: 0.00580 AC: 350 AN: 60378

GnomAD4 genome AF: 0.0256 AC: 3900 AN: 152358 Hom.: 164 Cov.: 34 AF XY: 0.0240 AC XY: 1786 AN XY: 74502

African (AFR) AF: 0.0885 AC: 3680 AN: 41578

American (AMR) AF: 0.00856 AC: 131 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68030

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0126 Hom.: 39

Bravo AF: 0.0285

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.55
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74161742; hg19: chr10-134040319;