chr5-160253613-C-T

Variant summary

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

The NM_001308173.3(CCNJL):​c.929G>A​(p.Arg310Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,326 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R310W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CCNJL
NM_001308173.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98
Variant links:
Genes affected
CCNJL (HGNC:25876): (cyclin J like) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in centrosome; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.074251324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNJLNM_001308173.3 linkc.929G>A p.Arg310Gln missense_variant Exon 6 of 6 ENST00000257536.13 NP_001295102.1 Q8IV13B4DZA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNJLENST00000257536.13 linkc.929G>A p.Arg310Gln missense_variant Exon 6 of 6 2 NM_001308173.3 ENSP00000257536.7 B4DZA8

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152054
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000387
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248348
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134698
show subpopulations
Gnomad AFR exome
AF:
0.000388
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS 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:
0.0000363
AC:
53
AN:
1461272
Hom.:
0
Cov.:
31
AF XY:
0.0000426
AC XY:
31
AN XY:
726864
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152054
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.000387
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.000106
ExAC
AF:
0.0000413
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1073G>A (p.R358Q) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the arginine (R) at amino acid position 358 to be replaced by a glutamine (Q). 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
0.081
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0027
T;.;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.82
T;.;T;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.074
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L;.;.;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.44
N;N;.;.
REVEL
Benign
0.039
Sift
Benign
0.25
T;T;.;.
Sift4G
Benign
0.71
T;T;.;T
Polyphen
0.28
B;B;B;.
Vest4
0.045
MVP
0.18
MPC
0.30
ClinPred
0.026
T
GERP RS
4.3
Varity_R
0.052
gMVP
0.33

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.

Other links and lift over

dbSNP: rs779603501; hg19: chr5-159680620; API