chr10-6464401-T-G

Variant names:

• chr10-6464401-T-G
• rs528116073
• NM_006257.5:c.1357A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

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]

ENSG00000302067 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1074484).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006257.5. 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
	PRKCQ	NM_006257.5	MANE Select	c.1357A>C	p.Asn453His	missense	Exon 13 of 18	NP_006248.1	Q04759-1
	PRKCQ	NM_001323265.1		c.1357A>C	p.Asn453His	missense	Exon 13 of 18	NP_001310194.1	Q04759-1
	PRKCQ	NM_001282644.2		c.1249A>C	p.Asn417His	missense	Exon 13 of 18	NP_001269573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	ENST00000263125.10	TSL:1 MANE Select	c.1357A>C	p.Asn453His	missense	Exon 13 of 18	ENSP00000263125.5	Q04759-1
	PRKCQ	ENST00000915286.1		c.1357A>C	p.Asn453His	missense	Exon 13 of 18	ENSP00000585345.1
	PRKCQ	ENST00000866196.1		c.1357A>C	p.Asn453His	missense	Exon 13 of 18	ENSP00000536255.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000129 AC: 3 AN: 232612 AF XY: 0.0000237

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000762 AC: 11 AN: 1443226 Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9 AN XY: 718520

African (AFR) AF: 0.00 AC: 0 AN: 31880

American (AMR) AF: 0.00 AC: 0 AN: 37422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.000132 AC: 11 AN: 83604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106740

Other (OTH) AF: 0.00 AC: 0 AN: 59630

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.11
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.46	N
PhyloP100		2.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.12
Sift	Benign	0.66	T
Sift4G	Benign	0.66	T
Polyphen		0.64	P
Vest4		0.35
MutPred		0.56		Gain of sheet (P = 0.0827)
MVP		0.58
MPC		0.48
ClinPred		0.079	T
GERP RS		5.2
Varity_R		0.25
gMVP		0.71
Mutation Taster		=65/35	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: rs528116073; hg19: chr10-6506363;