chr10-132208071-T-C

Position:

• chr10-132208071-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_173575.4(STK32C):​c.1400A>G​(p.Glu467Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,310,958 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E467K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: STK32C NM_173575.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032665431).
• BP6: Variant 10-132208071-T-C is Benign according to our data. Variant chr10-132208071-T-C is described in ClinVar as [Benign]. Clinvar id is 783587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00471 (718/152352) while in subpopulation AFR AF= 0.0164 (683/41590). AF 95% confidence interval is 0.0154. There are 4 homozygotes in gnomad4. There are 336 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• 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.1400A>G	p.Glu467Gly	missense_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.1400A>G	p.Glu467Gly	missense_variant	12/12	1	NM_173575.4	ENSP00000298630.3
STK32C	ENST00000368622.5	c.1049A>G	p.Glu350Gly	missense_variant	12/12	1		ENSP00000357611.1
STK32C	ENST00000462160.5	n.1287A>G		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152234 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00154 AC: 176 AN: 114260 Hom.: 0 AF XY: 0.000840 AC XY: 52 AN XY: 61894

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000131

Gnomad OTH exome AF: 0.000525

GnomAD4 exome AF: 0.000513 AC: 594 AN: 1158606 Hom.: 3 Cov.: 31 AF XY: 0.000436 AC XY: 242 AN XY: 554796

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00471 AC: 718 AN: 152352 Hom.: 4 Cov.: 34 AF XY: 0.00451 AC XY: 336 AN XY: 74500

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00334 Hom.: 0

Bravo AF: 0.00528

ESP6500AA AF: 0.0155 AC: 68

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00171 AC: 193

Asia WGS AF: 0.000866 AC: 3 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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0082	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.29	T;T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.080
Sift	Benign	0.055	T;D
Sift4G	Benign	0.26	T;T
Polyphen		0.56	P;B
Vest4		0.17
MVP		0.64
MPC		0.27
ClinPred		0.014	T
GERP RS		0.86
Varity_R		0.056
gMVP		0.19

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: rs143819270; hg19: chr10-134021575;