Variant 10-132222910-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173575.4(STK32C):c.1070T>C(p.Leu357Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,414,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.151

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079084724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK32C	NM_173575.4 link	c.1070T>C	p.Leu357Pro	missense_variant	9/12	ENST00000298630.8	NP_775846.2	Q86UX6-1A0A140VJW0B7Z7J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STK32C	ENST00000298630.8 link	c.1070T>C	p.Leu357Pro	missense_variant	9/12	1	NM_173575.4	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5 link	c.719T>C	p.Leu240Pro	missense_variant	9/12	1		ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000462160.5 link	n.887T>C		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

177746

Hom.:

AF XY:

0.0000208

AC XY:

AN XY:

96076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000495

AC:

AN:

1414092

Hom.:

Cov.:

AF XY:

0.00000571

AC XY:

AN XY:

700190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000641

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.1070T>C (p.L357P) alteration is located in exon 9 (coding exon 9) of the STK32C gene. This alteration results from a T to C substitution at nucleotide position 1070, causing the leucine (L) at amino acid position 357 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.9

DANN

Benign

0.73

DEOGEN2

Benign

0.026

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.054

Sift

Benign

0.042

D;T

Sift4G

Uncertain

0.050

T;T

Polyphen

0.0010

B;B

Vest4

0.15

MVP

0.10

MPC

0.36

ClinPred

0.035

GERP RS

-1.4

Varity_R

0.061

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over