10-132208130-G-C

Position:

• chr10-132208130-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_173575.4(STK32C):​c.1341C>G​(p.Leu447Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,310,714 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 35)
  • Exomes 𝑓: 0.0049 (21 hom.)
• Consequence: STK32C NM_173575.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.202

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-132208130-G-C is Benign according to our data. Variant chr10-132208130-G-C is described in ClinVar as [Benign]. Clinvar id is 708796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.202 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK32C	NM_173575.4	c.1341C>G	p.Leu447Leu	synonymous_variant	12/12	ENST00000298630.8	NP_775846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK32C	ENST00000298630.8	c.1341C>G	p.Leu447Leu	synonymous_variant	12/12	1	NM_173575.4	ENSP00000298630.3
STK32C	ENST00000368622.5	c.990C>G	p.Leu330Leu	synonymous_variant	12/12	1		ENSP00000357611.1
STK32C	ENST00000462160.5	n.1228C>G		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 661 AN: 152266 Hom.: 4 Cov.: 35

Gnomad AFR AF: 0.000747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00791

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00542

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00571 AC: 655 AN: 114756 Hom.: 4 AF XY: 0.00578 AC XY: 360 AN XY: 62312

Gnomad AFR exome AF: 0.000428

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.00697

Gnomad OTH exome AF: 0.00466

GnomAD4 exome AF: 0.00494 AC: 5718 AN: 1158330 Hom.: 21 Cov.: 31 AF XY: 0.00513 AC XY: 2847 AN XY: 554488

Gnomad4 AFR exome AF: 0.000562

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.000328

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.00518

Gnomad4 OTH exome AF: 0.00448

GnomAD4 genome AF: 0.00432 AC: 659 AN: 152384 Hom.: 4 Cov.: 35 AF XY: 0.00474 AC XY: 353 AN XY: 74514

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00542

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00450 Hom.: 1

Bravo AF: 0.00400

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.57

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: rs146688423; hg19: chr10-134021634;