dbSNP rs577074026: STK32C:p.Val313Leu (chr10-132224463-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173575.4(STK32C):c.937G>T(p.Val313Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,420,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V313M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

Publications

1 publications found

Variant links:

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]

STK32C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17041492).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK32C	NM_173575.4	MANE Select	c.937G>T	p.Val313Leu	missense	Exon 8 of 12	NP_775846.2
STK32C	NM_001318878.2		c.976G>T	p.Val326Leu	missense	Exon 8 of 12	NP_001305807.1	B7Z7J1
STK32C	NM_001318879.2		c.586G>T	p.Val196Leu	missense	Exon 8 of 12	NP_001305808.1	Q86UX6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK32C	ENST00000298630.8	TSL:1 MANE Select	c.937G>T	p.Val313Leu	missense	Exon 8 of 12	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5	TSL:1	c.586G>T	p.Val196Leu	missense	Exon 8 of 12	ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000916800.1		c.961G>T	p.Val321Leu	missense	Exon 8 of 12	ENSP00000586859.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000536

AC:

AN:

186426

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000364

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1420178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702258

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32754

American (AMR)

AF:

0.0000262

AC:

AN:

38220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25320

East Asian (EAS)

AF:

0.00

AC:

AN:

37806

South Asian (SAS)

AF:

0.00

AC:

AN:

80592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090804

Other (OTH)

AF:

0.00

AC:

AN:

58926

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.13

PhyloP100

4.1

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.0

REVEL

Benign

0.051

Sift

Benign

0.16

Sift4G

Benign

0.29

Polyphen

0.0080

Vest4

0.30

MVP

0.55

MPC

0.25

ClinPred

0.35

GERP RS

3.1

Varity_R

0.23

gMVP

0.68

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over