rs201691454

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308173.3(CCNJL):​c.808G>T​(p.Gly270Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,568,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CCNJL
NM_001308173.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052103102).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNJLNM_001308173.3 linkc.808G>T p.Gly270Cys 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.808G>T p.Gly270Cys missense_variant Exon 6 of 6 2 NM_001308173.3 ENSP00000257536.7 B4DZA8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152138
Hom.:
0
Cov.:
33
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:
0.000580
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:
0.0000285
AC:
6
AN:
210694
Hom.:
0
AF XY:
0.0000351
AC XY:
4
AN XY:
113934
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000289
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000102
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000325
AC:
46
AN:
1416736
Hom.:
0
Cov.:
31
AF XY:
0.0000286
AC XY:
20
AN XY:
699986
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00115
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.17e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000582
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000331
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.952G>T (p.G318C) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a G to T substitution at nucleotide position 952, causing the glycine (G) at amino acid position 318 to be replaced by a cysteine (C). 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
0.096
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0041
T;.;.;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.63
T;.;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.052
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.;.;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.4
N;N;.;.
REVEL
Benign
0.054
Sift
Benign
0.044
D;T;.;.
Sift4G
Uncertain
0.017
D;T;.;D
Polyphen
1.0
D;P;P;.
Vest4
0.24
MVP
0.22
MPC
0.76
ClinPred
0.12
T
GERP RS
-4.1
Varity_R
0.086
gMVP
0.43

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: rs201691454; hg19: chr5-159680741; COSMIC: COSV57444539; COSMIC: COSV57444539; API