chr10-6464401-T-G

Position:

chr10-6464401-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006257.5(PRKCQ):c.1357A>C(p.Asn453His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,595,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

PRKCQ
NM_006257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

PRKCQ (HGNC:9410): (protein kinase C theta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. [provided by RefSeq, Jul 2008]

PRKCQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1074484).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCQ	NM_006257.5 linkuse as main transcript	c.1357A>C	p.Asn453His	missense_variant	13/18	ENST00000263125.10	NP_006248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCQ	ENST00000263125.10 linkuse as main transcript	c.1357A>C	p.Asn453His	missense_variant	13/18	1	NM_006257.5	ENSP00000263125	P1	Q04759-1
PRKCQ	ENST00000397176.6 linkuse as main transcript	c.1357A>C	p.Asn453His	missense_variant	13/17	5		ENSP00000380361		Q04759-2
PRKCQ	ENST00000539722.5 linkuse as main transcript	c.982A>C	p.Asn328His	missense_variant	12/17	2		ENSP00000441752		Q04759-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232612

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

126466

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:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000762

AC:

AN:

1443226

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

718520

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:

0.000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

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

Apr 04, 2023

The c.1357A>C (p.N453H) alteration is located in exon 1 (coding exon 1) of the PRKCQ gene. This alteration results from a A to C substitution at nucleotide position 1357, causing the asparagine (N) at amino acid position 453 to be replaced by a histidine (H). 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

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.0064

T;T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

.;N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

3.5

.;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.66

.;T;T;T

Sift4G

Benign

0.66

T;T;T;T

Polyphen

0.64, 0.0010

.;P;B;.

Vest4

0.35

MutPred

0.56

.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;

MVP

0.58

MPC

0.48

ClinPred

0.079

GERP RS

5.2

Varity_R

0.25

gMVP

0.71

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