NM_173575.4:c.1400A>G

Variant names:

• chr10-132208071-T-C
• rs143819270
• NM_173575.4:c.1400A>G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.1400A>G	p.Glu467Gly	missense	Exon 12 of 12	NP_775846.2
	STK32C	NM_001318878.2		c.1439A>G	p.Glu480Gly	missense	Exon 12 of 12	NP_001305807.1	B7Z7J1
	STK32C	NM_001318879.2		c.1049A>G	p.Glu350Gly	missense	Exon 12 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.1400A>G	p.Glu467Gly	missense	Exon 12 of 12	ENSP00000298630.3	Q86UX6-1
	STK32C	ENST00000368622.5	TSL:1	c.1049A>G	p.Glu350Gly	missense	Exon 12 of 12	ENSP00000357611.1	Q86UX6-2
	STK32C	ENST00000916800.1		c.1424A>G	p.Glu475Gly	missense	Exon 12 of 12	ENSP00000586859.1

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

GnomAD2 exomes AF: 0.00154 AC: 176 AN: 114260 AF XY: 0.000840

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 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

African (AFR) AF: 0.0165 AC: 411 AN: 24912

American (AMR) AF: 0.00104 AC: 18 AN: 17248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15272

East Asian (EAS) AF: 0.00 AC: 0 AN: 30462

South Asian (SAS) AF: 0.00 AC: 0 AN: 26702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39738

Middle Eastern (MID) AF: 0.00113 AC: 5 AN: 4436

European-Non Finnish (NFE) AF: 0.000101 AC: 96 AN: 953604

Other (OTH) AF: 0.00138 AC: 64 AN: 46232

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

African (AFR) AF: 0.0164 AC: 683 AN: 41590

American (AMR) AF: 0.000980 AC: 15 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00351 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

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
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
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.080
Sift	Benign	0.055	T
Sift4G	Benign	0.26	T
Polyphen		0.56	P
Vest4		0.17
MVP		0.64
MPC		0.27
ClinPred		0.014	T
GERP RS		0.86
Varity_R		0.056
gMVP		0.19
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs143819270; hg19: chr10-134021575;