chr10-132226815-G-A

Position:

• chr10-132226815-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK32C	NM_173575.4	c.624C>T	p.Arg208Arg	synonymous_variant	4/12	ENST00000298630.8	NP_775846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK32C	ENST00000298630.8	c.624C>T	p.Arg208Arg	synonymous_variant	4/12	1	NM_173575.4	ENSP00000298630.3
STK32C	ENST00000368622.5	c.273C>T	p.Arg91Arg	synonymous_variant	4/12	1		ENSP00000357611.1
STK32C	ENST00000462160.5	n.441C>T		non_coding_transcript_exon_variant	4/13	2
STK32C	ENST00000368620.2	c.*5C>T		downstream_gene_variant		3		ENSP00000357609.3

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

GnomAD3 exomes AF: 0.00648 AC: 1622 AN: 250116 Hom.: 65 AF XY: 0.00455 AC XY: 617 AN XY: 135616

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 SAS exome AF: 0.000294

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

Gnomad4 AFR exome AF: 0.0894

Gnomad4 AMR exome AF: 0.00517

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000430

Gnomad4 OTH exome AF: 0.00580

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

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0119 Hom.: 31

Bravo AF: 0.0285

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs74161742; hg19: chr10-134040319;