1-2111641-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002744.6(PRKCZ):​c.335-23621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,132 control chromosomes in the GnomAD database, including 5,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5305 hom., cov: 32)
Exomes 𝑓: 0.22 ( 5 hom. )

Consequence

PRKCZ
NM_002744.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Publications

10 publications found
Variant links:
Genes affected
PRKCZ (HGNC:9412): (protein kinase C zeta) Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKCZNM_002744.6 linkc.335-23621T>G intron_variant Intron 4 of 17 ENST00000378567.8 NP_002735.3 Q05513-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKCZENST00000378567.8 linkc.335-23621T>G intron_variant Intron 4 of 17 1 NM_002744.6 ENSP00000367830.3 Q05513-1

Frequencies

GnomAD3 genomes
AF:
0.259
AC:
39412
AN:
151898
Hom.:
5294
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.214
Gnomad AMI
AF:
0.272
Gnomad AMR
AF:
0.339
Gnomad ASJ
AF:
0.310
Gnomad EAS
AF:
0.248
Gnomad SAS
AF:
0.276
Gnomad FIN
AF:
0.299
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.261
Gnomad OTH
AF:
0.264
GnomAD4 exome
AF:
0.216
AC:
25
AN:
116
Hom.:
5
Cov.:
0
AF XY:
0.239
AC XY:
21
AN XY:
88
show subpopulations
African (AFR)
AF:
0.333
AC:
2
AN:
6
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4
South Asian (SAS)
AF:
0.00
AC:
0
AN:
6
European-Finnish (FIN)
AF:
0.167
AC:
1
AN:
6
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.220
AC:
18
AN:
82
Other (OTH)
AF:
0.333
AC:
4
AN:
12
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.535
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.259
AC:
39445
AN:
152016
Hom.:
5305
Cov.:
32
AF XY:
0.263
AC XY:
19545
AN XY:
74310
show subpopulations
African (AFR)
AF:
0.213
AC:
8856
AN:
41488
American (AMR)
AF:
0.339
AC:
5180
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.310
AC:
1075
AN:
3464
East Asian (EAS)
AF:
0.249
AC:
1285
AN:
5156
South Asian (SAS)
AF:
0.275
AC:
1324
AN:
4808
European-Finnish (FIN)
AF:
0.299
AC:
3168
AN:
10586
Middle Eastern (MID)
AF:
0.150
AC:
44
AN:
294
European-Non Finnish (NFE)
AF:
0.261
AC:
17703
AN:
67920
Other (OTH)
AF:
0.267
AC:
563
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1486
2972
4459
5945
7431
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
410
820
1230
1640
2050
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.265
Hom.:
3316
Bravo
AF:
0.262
Asia WGS
AF:
0.221
AC:
768
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.6
DANN
Benign
0.40
PhyloP100
-1.8
PromoterAI
-0.013
Neutral
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs6603813; hg19: chr1-2043080; API