10-132220875-A-G

Position:

• chr10-132220875-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173575.4(STK32C):​c.1251+1766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,148 control chromosomes in the GnomAD database, including 46,540 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46540 hom., cov: 32)
• Consequence: STK32C NM_173575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK32C	NM_173575.4	c.1251+1766T>C		intron_variant		ENST00000298630.8	NP_775846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK32C	ENST00000298630.8	c.1251+1766T>C		intron_variant		1	NM_173575.4	ENSP00000298630.3
STK32C	ENST00000368622.5	c.900+1766T>C		intron_variant		1		ENSP00000357611.1
STK32C	ENST00000462160.5	n.1068+1766T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118573 AN: 152030 Hom.: 46498 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.780 AC: 118677 AN: 152148 Hom.: 46540 Cov.: 32 AF XY: 0.782 AC XY: 58164 AN XY: 74404

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.784

Alfa AF: 0.792 Hom.: 61979

Bravo AF: 0.784

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2035804; hg19: chr10-134034379;