Genetic Variant CCNJL:p.Thr274Pro (chr5-160253722-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308173.3(CCNJL):c.820A>C(p.Thr274Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCNJL
NM_001308173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.480

Publications

1 publications found

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]

CCNJL links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065259546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNJL	NM_001308173.3 link	c.820A>C	p.Thr274Pro	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
CCNJL	ENST00000257536.13 link	c.820A>C	p.Thr274Pro	missense_variant	Exon 6 of 6	2	NM_001308173.3	ENSP00000257536.7		B4DZA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1431214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708928

African (AFR)

AF:

0.00

AC:

AN:

33010

American (AMR)

AF:

0.00

AC:

AN:

42364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24450

East Asian (EAS)

AF:

0.00

AC:

AN:

39282

South Asian (SAS)

AF:

0.00

AC:

AN:

82322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097676

Other (OTH)

AF:

0.00

AC:

AN:

59164

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.964A>C (p.T322P) alteration is located in exon 7 (coding exon 6) of the CCNJL gene. This alteration results from a A to C substitution at nucleotide position 964, causing the threonine (T) at amino acid position 322 to be replaced by a proline (P). 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

0.058

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.1

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.000090

T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.46

T;.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;.;.

PhyloP100

-0.48

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.020

N;N;.;.

REVEL

Benign

0.011

Sift

Benign

0.23

T;T;.;.

Sift4G

Benign

0.10

T;T;.;T

Polyphen

0.0

B;B;B;.

Vest4

0.11

MutPred

0.50

Loss of sheet (P = 0.0054);.;.;.;

MVP

0.055

MPC

0.32

ClinPred

0.039

GERP RS

-1.3

Varity_R

0.060

gMVP

0.41

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over